Reproduction 26 and Development Sex Determination Sex Determine Genetic Sex Sexual Diff erentiation Occurs Early in Development Basic Patterns of Reproduction Begins in Utero The Brain Directs Reproduction Environmental Factors Infl uence Reproduction Male Reproduction Testes Produce and Requires Gonadotropins and Testosterone Male Accessory Glands Contribute Secretions to Semen Infl uence Secondary Sex Characteristics Female Reproduction Females Have an Internal Uterus The Ovary Produces and Hormones A Lasts about One Month Hormonal Control of the Menstrual Cycle Is Complex Hormones Infl uence Female Secondary Sex Characteristics Procreation The Sexual Response Has Four Phases The Male Sex Act Includes and , and copulation, Sexual Dysfunction Aff ects Males and Females and . That’s all Contraceptives Are Designed to Prevent the facts when you Infertility Is the Inability to Conceive come to brass tacks. Pregnancy and Parturition —T.S. Eliot, Sweeney Agonistes Fertilization Requires The Developing Implants in the Endometrium The Placenta Secretes Hormones During Pregnancy Background Basics Pregnancy Ends with Labor and Delivery Positive and negative The Mammary Glands Secrete Milk During feedback Prolactin Has Other Physiological Roles Flagella Steroids Growth and Aging Agonist/antagonist Marks the Beginning of the Reproductive Years Up-and down-regulation and Andropause Are a Consequence of Aging Prostaglandins Hypothalamic-pituitary axis Prolactin Oxytocin Cross-section Spinal refl ex of intestinal villi Hot fl ashes (outlined in red).

900 Reproduction and Development

magine growing up as a , then at the age of 12 or so, Sex hormones play a significant role in the behavior of fi nding that your voice is deepening and your genitals are other mammals, acting on as well as infl uencing the brain Ideveloping into those of a man. Th is scenario actually hap- of the developing embryo. Th eir role in is more con- pens to a small number of men who have a condition known troversial. Human are exposed to sex hormones while in as pseudohermaphroditism {pseudes, false + hermaphrodites, the the uterus, but it is unclear how much infl uence these hormones dual-sex off spring of Hermes and Aphrodite}. Th ese men have have on behavior later in life. Does the preference of little the internal sex organs of a male but inherit a gene that causes for dolls and of little boys for toy guns have a biological basis or a defi ciency in one of the male hormones. Consequently, they a cultural basis? We have no answer yet, but growing evidence are born with external genitalia that appear feminine, and they suggests that at least part of our brain structure is infl uenced by are raised as girls. At puberty { pubertas, adulthood}, the period sex hormones before we ever leave the womb. when a person makes the transition from being nonreproduc- In this chapter we address the biology of human reproduc- tive to being reproductive, pseudohermaphrodites begin to se- tion and development. We begin our discussion with that crete more male hormones. As a result, they develop some, but fuse to form the fertilized , or . As the zygote begins to not all, of the characteristics of men. Not surprisingly, a con- divide (2-cell stage, 4-cell stage, etc.), it becomes fi rst an embryo fl ict arises: should these individuals change gender or remain (weeks 0–8 of development), then a (8 weeks until birth). female? Most choose to change and continue life as men. Reproduction is one area of physiology in which we hu- mans like to think of ourselves as signifi cantly advanced over Sex Determination other animals. We mate for pleasure as well as procreation, and The male and female sex organs consist of three sets of struc- women are always sexually receptive (that is, not only during tures: the gonads, the internal genitalia, and the external genita- fertile periods). But just how diff erent are we? lia. Gonads { gonos, seed} are the organs that produce gametes Like many other terrestrial animals, humans have internal {gamein, to marry}, the eggs and sperm that unite to form a new fertilization that allows motile fl agellated sperm to remain in an individual. Th e male gonads are the testes (singular testis), which aqueous environment. To facilitate the process, we have mating produce sperm ( spermatozoa ). Th e female gonads are the ova- and courtship rituals, as do other animals. Development is also ries, which produce eggs, or ova (singular ovum ). Th e undiff eren- internal, within the uterus, which protects the growing embryo 26 tiated gonadal cells destined to produce eggs and sperm are called from dehydration and cushions it in a layer of fl uid. germ cells. Th e internal genitalia consist of accessory glands and Humans are sexually dimorphic { di-, two + morphos , ducts that connect the gonads with the outside environment. Th e form}, meaning that males and females are physically distinct. external genitalia include all external reproductive structures. This distinction is sometimes blurred by dress and hairstyle, Sexual development is programmed in the human genome. but these are cultural acquisitions. Although everyone agrees Each nucleated cell of the body except eggs and sperm contains that male and female humans are physically dimorphic, we are 46 chromosomes. Th is set of chromosomes is called the diploid still debating whether we are behaviorally and psychologically number because the chromosomes occur in pairs: 22 matched, dimorphic as well. or homologous, pairs of autosomes plus one pair of sex chromo- somes ( Fig. 26.1 a). Th e 22 pairs of autosomal chromosomes RUNNING PROBLEM direct development of the form and of variable characteristics such as hair color and blood type. Th e two sex Infertility chromosomes, designated as either X or Y, contain genes that Peggy and Larry have just about everything to make them direct development of internal and external sex organs. Th e X happy: successful careers, a loving marriage, a comfortable is larger than the Y chromosome and includes home. But one thing is missing: after fi ve years of marriage, many genes that are missing from the Y chromosome. they have been unable to have a . Today, Peggy and Eggs and sperm are haploid cells with 23 chromosomes, Larry have their fi rst appointment with Dr. Coddington, an one from each matched pair and one sex chromosome. When infertility specialist. “Finding the cause of your infertility egg and sperm unite, the resulting zygote then contains a unique is going to require some painstaking detective work,” set of 46 chromosomes, with one chromosome of each matched Dr. Coddington explains. He will begin his workup of pair coming from the mother and the other from the father. Peggy and Larry by asking detailed questions about their reproductive histories. Based on the answers to these questions, he will then order tests to pinpoint the problem. Sex Chromosomes Determine Genetic Sex Th e sex chromosomes a person inherits determine the genetic sex of that individual. Genetic females are XX, and genetic males are XY ( Fig. 26.1 b). Females inherit one X chromosome from

901 Reproduction and Development

whether development proceeds along male or female lines. Th e HUMAN CHROMOSOMES presence of a Y chromosome means the embryo will become (a) Humans have 23 pairs of chromosomes: 22 pairs of autosomes male, even if the zygote also has multiple X chromosomes. For and one pair of sex chromosomes. X and Y chromosomes (lower instance, an XXY zygote will become male. A zygote that in- right) mean that these chromosomes came from a male. The autosomes are arranged in homologous pairs in this figure. herits only a Y chromosome (YO) will die because the larger X chromosome contains essential genes that are missing from the Y chromosome. In the absence of a Y chromosome, an embryo will de- velop into a female. For this reason, a zygote that gets only one X chromosome (XO; Turner’s syndrome) will develop into a fe- male. Two X chromosomes are needed for normal female repro- ductive function, however. Once the ovaries develop in a female fetus, one X chromo- some in each cell of her body inactivates and condenses into a clump of nuclear chromatin known as a Barr body. (Barr bodies in females can be seen in stained cheek epithelium.) Th e selec- tion of the X chromosome that becomes inactive during devel- opment is random: some cells will have an active maternal X chromosome and others have an active paternal X chromosome. Because inactivation occurs early in development—before cell division is complete—all cells of a given tissue will usually have the same active X chromosome, either maternal or paternal.

Concept Check Answers: End of Chapter 1. Name the male and female gonads and gametes.

(b) X and Y chromosomes determine sex. Each egg produced by a female (XX) has an X chromosome. Sperm produced by a male (XY) have either an X chromosome or a Y chromosome. Sexual Diff erentiation Occurs Early in Development Female parent Male parent The sex of an early embryo is difficult to determine because XX XY reproductive structures do not begin to diff erentiate until the seventh week of development. Before diff erentiation, the embry- onic tissues are considered bipotential because they cannot be morphologically identifi ed as male or female. The bipotential gonad has an outer cortex and an inner XXEggs X Sperm Y medulla ( Fig. 26.2 a). Under the infl uence of the appropriate developmental signal (described below), the medulla will de- velop into a testis. In the absence of that signal, the cortex will XX Female offspring diff erentiate into ovarian tissue. The bipotential internal genitalia consist of two pairs of accessory ducts: Wolffian ducts (mesonephric) derived from the embryonic kidney, and Müllerian ducts (paramesonephric XY Male offspring ducts) . As development proceeds along either male or female Fig. 26.1 lines, one pair of ducts develops while the other degenerates (Fig. 26.2 a 2 ). The bipotential external genitalia consist of a genital tu- each parent. Males inherit a Y chromosome from the father and bercle, urethral folds, urethral groove, and labioscrotal swellings an X chromosome from the mother. Th e Y chromosome is es- ( Fig. 26.2 b). These structures differentiate into the male and sential for development of the male reproductive organs. female reproductive structures as development progresses. If sex chromosomes are abnormally distributed at fertiliza- What directs some single-cell to become males, tion, the presence or absence of a Y chromosome determines and others to become females? Sex determination depends on

902 Reproduction and Development

the opening of this chapter. Th ese men inherit a defective gene CLINICAL FOCUS for 5a -reductase, the enzyme that catalyzes the conversion of testosterone to DHT ( Fig. 26.4 ). Despite normal testosterone X-Linked Inherited Disorders secretion, these men have inadequate levels of DHT, and as a re- Normally, a person inherits two copies of the gene sult the male external genitalia and prostate gland fail to develop for a given trait: one copy from each parent. However, many fully during fetal development. genes found on the X chromosome, called X-linked genes , At birth, the appear to be female and are raised have no matching gene on the much smaller Y chromosome. as such. However, at puberty, the testes again begin to secrete Females always get two copies of X-linked genes, so the testosterone, causing masculinization of the external genitalia, expression of X-linked traits follows the usual pattern of gene pubic hair growth (although scanty facial and body hair), and dominance and recession. Males, however, receive only one deepening voice. By studying the 5a-reductase defect in these copy of an X-linked gene—on the X chromosome from their individuals, scientists have been able to separate the eff ects of mother—so males always exhibit the traits associated with testosterone from those of DHT. an X-linked gene. If the maternally inherited X-linked gene is Exposure of nongenital tissues to testosterone during em- defective, male off spring will exhibit the mutation. Among bryonic development is known to have masculinizing eff ects, the identifi ed X-linked diseases are Duchenne muscular such as altering the brain’s responsiveness to certain hormones. dystrophy, hemophilia, and color-blindness. One controversial aspect of the masculinizing eff ects of testos- terone is its influence on human sexual behavior and gender identity. It is well documented that in many nonhuman mam- the presence or absence of the s ex-determining r egion of the Y mals, sexual behavior depends on the absence or presence chromosome, or SRY gene. In the presence of a functional SRY of testosterone during critical periods of brain development. gene, the bipotential gonads develop into testes. In the absence However, a similar cause-effect relationship has never been of the SRY gene and under the direction of multiple female- proved in humans. In human behavior, it is very difficult to specifi c genes, the gonads develop into ovaries. separate biological infl uences from environmental factors, and it will probably be years before this question is resolved. Male Th e SRY gene produces a pro- 26 tein (testis-determining factor or TDF ) that binds to DNA and Female Embryonic Development In female , which activates additional genes, including SOX9, WT1 (Wilms’ tu- have no SRY gene, the cortex of the bipotential gonad devel- mor protein), and SF1 (steroidogenic factor). Th e protein prod- ops into ovarian tissue ( Fig. 26.2 a 1 female). Research indi- ucts of these genes direct development of the gonadal medulla cates that female development is more complex than originally into a testis ( Fig. 26.3 ). Note that testicular development does thought, with multiple genes required for the development of not require male sex hormones such as testosterone. Th e devel- functional ovaries. oping embryo cannot secrete testosterone until aft er the gonads In the absence of testicular AMH, the Müllerian ducts diff erentiate into testes. develop into the upper portion of the vagina, the uterus, and Once the testes diff erentiate, they begin to secrete three the fallopian tubes, named aft er the anatomist Fallopius, who hormones that infl uence development of the male internal and fi rst described them (Fig. 26.2 a 3 female). Fallopian tubes are external genitalia. Testicular Sertoli cells secrete glycopro- also called oviducts. Without testosterone, the Wolffi an ducts tein anti-Müllerian (AMH; also called Müllerian- degenerate ( Fig. 26.2 a 2 female). Without DHT, the external inhibiting substance). Testicular Leydig cells secrete testosterone genitalia take on female characteristics (Fig. 26.2 b). and its derivative dihydrotestosterone (DHT). Th ese two an- drogens { andro - , male} are the dominant steroid hormones in males. Testosterone and DHT both bind to the same Answers: End of chapter receptor, but the two ligands elicit diff erent responses. Concept Check In the developing fetus, anti-Müllerian hormone causes the 2 . Where in a target cell would you expect to fi nd receptors for embryonic Müllerian ducts to regress (Fig. 26.2 a, 2 male). Tes- androgens? Where would you expect to fi nd receptors for AMH? tosterone converts the Wolffi an ducts into male accessory struc- 3. Why was King Henry VIII of England wrong to blame his wives when tures: epididymis, vas deferens, and seminal vesicle ( 3 male). they were unable to produce a male heir to the throne? Later in fetal development, testosterone controls migration of the testes from the abdomen into the scrotum, or scrotal sac. Th e 4. Which sex will a zygote become if it inherits only one X chromosome (XO)? remaining male sex characteristics, such as diff erentiation of the 5. If the testes are removed from an early male embryo, why does it develop external genitalia, are controlled primarily by DHT. a uterus and fallopian tubes rather than the normal male accessory The importance of DHT in male development came to structures? Will the embryo have male or female external genitalia? Explain. light in studies of the male pseudohermaphrodites described in

903 (a) Development of Internal Organs

Bipotential stage: 6 week fetus The internal reproductive organs have the potential to develop into Bipotential stage male or female structures. (6 week fetus)

Müllerian duct Wolffian duct Gonad (bipotential) Kidney IF FEMALE: IF MALE:

Gonad (cortex) forms ovary. Gonad (cortex) regresses.

Gonad (medulla) regresses. Gonad (medulla) forms testis.

Wolffian duct regresses Wolffian duct forms epididymis, (testosterone absent). vas deferens, and seminal vesicle (testosterone present).

Müllerian duct becomes fallopian Cloacal opening Müllerian duct regresses tube, uterus, cervix, and upper (AMH present). 1/2 of vagina (AMH absent).

FEMALE MALE

10 weeks 10 weeks

Gonadal cortex 1 1 SRY protein in a male becomes ovary in the embryo directs the absence of SRY protein medulla of the and under the influence Testis bipotential gonad of female-specific genes. to develop into testis.

2 Absence of testosterone causes Wolffian duct 2 Anti-Müllerian hormone to degenerate. Müllerian duct Wolffian from testis causes the duct Müllerian ducts to disappear. Uterus

At birth At birth

Ovary

3 Absence of anti- Prostate 3 Testosterone from Müllerian hormone testis converts Wolffian allows the Seminal vesicle duct into seminal Müllerian duct (from Müllerian vesicle, vas deferens, to become the duct) Vas deferens and epididymis. DHT fallopian tube, controls prostate uterus, and upper Uterus development. part of the vagina. Testis

Vagina Epididymis

904 (b) Development of External Genitalia

Bipotential stage: The external genitalia of a 6-week fetus cannot be visually identified as male or female. Bipotential stage (6 week fetus) Genital tubercle

Urethral groove Labioscrotal swelling Urethral fold

IF FEMALE: IF MALE:

Genital tubercle forms clitoris. Genital tubercle forms glans penis.

Urethral folds and grooves Urethral folds and grooves form minora, opening Anus form shaft of penis. of vagina and urethra.

Labioscrotal swellings Labioscrotal swellings form labia majora. form shaft of penis and scrotum.

FEMALE MALE

10 weeks 10 weeks

Clitoris Penis 26 Urethral fold Urethral fold Labioscrotal swelling Labioscrotal swelling Anus Anus

1 In the absence 1 DHT causes of androgens, development the external genitalia of male external are feminized. genitalia.

At birth At birth

Glans penis Labia Clitoris majora Urethral opening Shaft of penis Labia Vaginal opening minora Scrotum Anus Anus 2 The testes descend from the abdominal cavity into the scrotum.

905 Reproduction and Development

The SRY gene directs male development. CLINICAL FOCUS

Determining Sex Sex-determining region of Y chromosome The fi rst question new parents typically ask about in embryonic germ their child is, “Is it a or a girl?” Sometimes the answer cells (SRY gene) is not obvious because in approximately 1 in 3000 , the sex of the child cannot easily be determined. Multiple produces criteria might be used to establish an individual’s sex: genetic, chromosomal, gonadal, morphological, or even psychological Testis-determining characteristics. For example, presence of a Y chromosome SRY protein with a functional SRY gene could be one criterion for “maleness.” However, it is possible for an to have a Y initiates production of chromosome and not appear to be male because of a defect in some aspect of development. Currently there is ongoing Multiple proteins that cause gonad medulla to debate about how best to decide sex in cases where there is differentiate into a testis doubt. Traditionally, sex determination has been based on appearance of the external genitalia at birth, but the idea which has that individuals should be allowed to choose their sex when they become old enough is gaining ground. The sex a person considers himself or herself to be is called the person’s gender Leydig Sertoli cells cells identity. You can read more about causes of ambiguous genitalia and the current criteria used to decide a child’s sex secrete secrete in the American Academy of Pediatrics policy statement “Evaluation of the Newborn with Developmental Anomalies Testosterone Anti-Müllerian of the External Genitalia,” Pediatrics 106(1): 138–142, 2000 hormone (July) (available online at http://pediatrics.aappublications.org ). controls causes

Development of Wolffian Regression of duct into accessory Müllerian duct SYNTHESIS PATHWAYS FOR STEROID HORMONES structures Development of male The blank boxes represent intermediate compounds external genitalia (via DHT) whose names have been omitted for simplicity.

Fig. 26.3 Cholesterol

Basic Patterns of Reproduction Th e testis and ovary both produce hormones and gametes, and they share other similarities, as might be expected of organs Progesterone having the same origin. However, male and female gametes are very diff erent from each other. Eggs are some of the larg- Dihydro- Testosterone * testosterone est cells in the body. They are nonmotile and must be moved (DHT) through the reproductive tract on currents created by smooth aromatase muscle contraction or the beating of cilia. Sperm, in contrast, are quite small. Th ey are the only fl agellated cells in the body Corticosterone Cortisol Estradiol and are highly motile so that they can swim up the female re- productive tract in their search for an egg to fertilize. Th e timing of production, or gametogenesis , is also KEY very diff erent in males and females. Most evidence indicates that * 5α-reductase women are born with all the eggs, or , they will ever have, Aldosterone although recent reports suggest there may be stem cells in the ovary. Intermediate steps During the reproductive years, eggs mature in a cyclic pattern and Fig. 26.4

906 Reproduction and Development are released from the ovaries roughly once a month. Aft er about has 23 single chromosomes, the haploid number char- 40 years, female reproductive cycles cease (menopause ). acteristic of a gamete 4 . Th e then mature into sperm. Men, in contrast, manufacture sperm continuously from the time they reach reproductive . Sperm production Female Gametogenesis In the embryonic ovary, germ cells and testosterone secretion diminish with age but do not cease as are called oögonia (singular oögonium ) ( Fig. 26.5 1 ). Oögonia women’s reproductive cycles do. complete and the DNA duplication stage of by the fi ft h month of fetal development 2 . At this time, mitosis ceases and no further oocytes can be formed. At birth Gametogenesis Begins in Utero each ovary contains about half a million primary gametes, or Figure 26.5 compares the male and female patterns of gameto- primary oocytes. genesis. In both sexes, germ cells in the embryonic gonads fi rst In the ovary, meiosis does not resume until puberty 3 . undergo a series of mitotic divisions to increase their numbers Each primary divides into two cells, a large egg ( sec- 1 . Aft er that, the germ cells are ready to undergo meiosis, the ondary oocyte) and a tiny first polar body. Despite the size cell division process that forms gametes. diff erence, the egg and polar body each contain 23 duplicated In the fi rst step of meiosis, the germ cell’s DNA replicates chromosomes. Th is fi rst polar body disintegrates. until each chromosome is duplicated (46 chromosomes du- Meanwhile, the egg begins the second meiotic division 4 . plicated = 92 chromosomes). The cell, now called a primary After the sister chromatids separate from each other, meiosis or primary oocyte, contains twice the normal pauses. Th e fi nal step of meiosis, in which sister chromatids go amount of DNA 2 . However, cell and chromosomal division to separate cells, does not take place unless the egg is fertilized. do not take place as they do in mitosis. Instead, each duplicated Th e ovary releases the mature egg during a process known chromosome forms two identical sister chromatids, linked as . If the egg is not fertilized, meiosis never goes to together at a region known as the centromere. The primary completion, and the egg disintegrates or passes out of the body gametes are then ready to undergo meiotic divisions to create 5 . If fertilization by a sperm occurs, the fi nal step of meiosis four haploid cells. takes place 6 . Half the sister chromatids remain in the fertilized In the first meiotic division , one primary gamete di- egg (zygote), while the other half are released in a second polar vides into two secondary gametes ( secondary spermatocyte or body. Th e second polar body, like the fi rst, degenerates. As a re- 26 secondary oocyte ) 3 . Each secondary gamete gets one copy sult of meiosis, each primary oocyte gives rise to only one egg. of each duplicated autosome plus one sex chromosome. In the Gametogenesis in both males and females is under the second meiotic division , the sister chromatids separate 4 . In control of hormones from the brain and from endocrine cells in males, the cells split during the second meiotic division, result- the gonads. Some of these hormones are identical in males and ing in two haploid sperm from each secondary spermatocyte. females, but others are diff erent. In females, the second meiotic division creates one egg and one small cell called a polar body . What happens aft er that de- Concept Check Answers: End of chapter pends on whether or not the egg is fertilized. Th e timing of mitotic and meiotic divisions is very diff er- 6. At what stage of development is the gamete in a newborn male? In a ent in males and females. Let’s take a closer look at gametogen- newborn female? esis in each sex. 7. Compare the amount of DNA in the fi rst polar body with the amount of DNA in the second polar body. Male Gametogenesis At birth, the testes of a newborn boy 8. How many gametes are formed from one primary oocyte? From one have not progressed beyond mitosis and contain only immature primary spermatocyte? germ cells ( Fig. 26.5 1 ). Aft er birth, the gonads become qui- escent (relatively inactive) until puberty, the period in the early teen years when the gonads mature. The Brain Directs Reproduction At puberty, germ cell mitosis resumes. From that point onward, the germ cells, known as spermatogonia (singu- Th e has some of the most complex control lar ), have two possible fates. Some continue pathways of the body, in which multiple hormones interact in an to undergo mitosis throughout the male’s reproductive life. ever-changing fashion. Th e pathways that regulate reproduction Others are destined to start meiosis and become primary begin with secretion of peptide hormones by the hypothalamus 2 . and anterior pituitary. Th ese trophic hormones control gonadal Each primary spermatocyte creates four sperm. In the fi rst secretion of the steroid sex hormones, including androgens, meiotic division, a primary spermatocyte divides into two sec- estrogens , and progesterone . ondary spermatocytes 3 . In the second meiotic division, each Th e sex steroids are closely related to one another and arise secondary spermatocyte divides into two spermatids. Each from the same steroid precursors ( Fig. 26.4 ). Both sexes produce

907 Reproduction and Development

GAMETOGENESIS

Germ cells first duplicate themselves through mitosis. Then, through meiosis, they form gametes with one chromosome from each pair. For simplicity, this figure shows only one of the body’s 22 pairs of autosomes in each cell.

Female Stage of Cell Division Male

1 MITOSIS Germ cell: Germ cell: Germ cell proliferation Oögonium Embryo Spermatogonium 46 chromosomes per cell (only two shown here) Embryo 46 .. (diploid) Oogonia Spermatogonia MEIOSIS 2 DNA replicates Primary but no cell division. Sister Primary oocyte Sister chromatids spermatocyte chromatids 46 chromosomes, duplicated Reproductive adult

3 First meiotic division First polar Secondary Primary gamete divides Secondary body oocyte (egg) into two secondary gametes. spermatocytes

(may not 23 chromosomes, occur) duplicated

4 Second meiotic Disintegrates adult Reproductive division Spermatids Secondary gamete divides. Egg released develop into from ovary at 23 chromosomes ovulation. (haploid) Sperm

6 One primary oocyte FERTILIZATION One primary spermatocyte yields 1 egg. yields 4 sperm.

5 Second polar body disintegrates.

Unfertilized egg passes out of body. Zygote Fig. 26.5

both androgens and estrogens, but androgens predominate in Some of the physiological eff ects attributed to testosterone are males, and estrogens are dominant in females. actually the result of DHT activity. In men, most testosterone is secreted by the testes, but Males synthesize some estrogens, but the feminizing eff ects about 5% comes from the adrenal cortex. Testosterone is con- of these compounds are usually not obvious in males. Both tes- verted in peripheral tissues to its more potent derivative DHT. tes and ovaries contain the enzyme aromatase, which converts

908 Reproduction and Development

HORMONAL CONTROL OF REPRODUCTION

(a) In both sexes, the brain controls reproduction through GnRH and pituitary gonadotropins (FSH and LH).

Internal and KEY CNS environmental Stimulus GnRH = gonadotropin- stimuli releasing hormone Integrating center

Output signal LH =

GnRH Target Hypothalamus Short-loop FSH = follicle-stimulating negative Tissue response hormone feedback

Anterior pituitary

(b) Feedback effects of sex steroids on gonadotropin release Long-loop feedback may be negative LH FSH or positive STEROID EFFECT GONADOTROPIN HORMONE LEVEL Fema Gonads Low estrogen Absence of Increases les o (ovaries or testes) or androgen negative feedback

Endocrine n cells ly Moderate estrogen Negative feedback Decreases or androgen Gamete 26 High androgen Negative feedback Decreases Steroid and production peptide hormones Sustained high Positive feedback Increases estrogen

Fig. 26.6 androgens to estrogens, the female sex hormones. A small ovary and testis secrete peptide hormones that feed back to act amount of estrogen is also made in peripheral tissues. directly on the pituitary. Inhibins inhibit FSH secretion, and re- In women, the ovary produces estrogens (particularly estra- lated peptides called activins stimulate FSH secretion. Activins diol and estrone ) and progestins , particularly progesterone. The also promote spermatogenesis, oocyte maturation, and devel- ovary and the adrenal cortex produce small amounts of androgens. opment of the embryonic nervous system. Th ese gonadal pep- tides are produced in nongonadal tissues as well, and their other Control Pathways Th e hormonal control of reproduction in both functions are still being investigated. sexes follows the basic hypothalamus-anterior pituitary-peripheral AMH, introduced earlier in the discussion of sexual gland pattern ( Fig. 26.6 ). Gonadotropin-releasing hormone differentiation during development, is also made by cells of (GnRH * ) from the hypothalamus controls secretion of two anterior both ovary and testis after birth. The inhibins, activins, and pituitary gonadotropins: follicle-stimulating hormone (FSH) AMH are part of a large family of related growth and differ- and luteinizing hormone (LH). FSH and LH in turn act on the entiation factors known as the transforming growth factor - b gonads. FSH, along with steroid sex hormones, is required to initi- family. ate and maintain gametogenesis. LH acts primarily on endocrine cells, stimulating production of the steroid sex hormones. Feedback Pathways Th e feedback loops of the reproductive Although primary control of gonadal function arises in system also become quite complex. Th e feedback pathways for the brain, the gonads also infl uence their own function. Both trophic hormones follow the general patterns for long-loop and short-loop feedback. Gonadal hormones alter secretion of GnRH, FSH, and LH in a long-loop response, and the pituitary * GnRH is sometimes called luteinizing hormone releasing hormone (LHRH) gonadotropins inhibit GnRH release from the hypothalamus by because it was fi rst thought to have its primary eff ect on LH. a short-loop path ( Fig. 26.6 a).

909 Reproduction and Development

When circulating levels of gonadal steroids are low, the pi- GnRH agonist creates chemical castration that reverses when tuitary secretes FSH and LH (Fig. 26.6 b). As steroid secretion the drug is no longer administered. increases, negative feedback usually inhibits gonadotropin re- lease. Androgens always maintain negative feedback on gonado- tropin release: as androgen levels go up, FSH and LH secretion Environmental Factors Infl uence Reproduction decreases. Among the least-understood infl uences on reproductive hor- However, in an unusual twist, higher concentrations of mones and gametogenesis are environmental eff ects. In men, estrogen can exert either positive or negative feedback. Low factors that influence gametogenesis are difficult to monitor levels of estrogen have no feedback eff ect. Moderate concentra- short of requesting periodic sperm counts. Disruption of the tions of estrogen have a negative feedback eff ect. But if estrogen normal reproductive cycle in women is easier to study because rises rapidly to a threshold level and remains high for at least physiological uterine bleeding in the menstrual cycle is easily 36 hours, feedback switches from negative to positive, and go- monitored. nadotropin release (particularly LH) is stimulated . Th e paradox- Factors that affect reproductive function in women in- ical eff ects of estrogen on gonadotropin release play a signifi cant clude stress, nutritional status, and changes in the day-night role in the female reproductive cycle, as you will learn later in cycle, such as those that occur with travel across time zones or this chapter. with shift work. Th e hormone melatonin from the pineal gland Scientists still do not fully understand the mechanism mediates reproduction in seasonally breeding animals, such as underlying the change from negative to positive feedback with birds and deer, and researchers are investigating whether mela- estrogen. Some evidence suggests that high levels of estrogen in- tonin also plays a role in seasonal and daily rhythms in humans. crease the number of GnRH receptors in the anterior pituitary, Environmental estrogens are also receiving a lot of atten- making it more sensitive to GnRH (up-regulation of receptors). tion. These are naturally occurring compounds, such as the Other evidence points to estrogen infl uencing GnRH release by phytoestrogens of plants, or synthetic compounds that have altering the release of a peptide called kisspeptin from hypotha- been released into the environment. Some of these com- lamic neurons. pounds bind to estrogen receptors in both sexes and mimic es- trogen’s eff ects. Others are anti-estrogens that block estrogen Pulsatile GnRH Release Tonic GnRH release from the hypo- receptors or interfere with second messenger pathways or pro- thalamus occurs in small pulses every 1–3 hours in both males tein synthesis. Growing evidence suggests that some of these and females. Th e region of the hypothalamus that contains the endocrine disruptors can adversely infl uence developing em- GnRH neuron cell bodies has been called a GnRH pulse gen- bryos and even have their eff ects passed down to subsequent erator because it coordinates the periodic pulsatile secretion of generations. GnRH. Now that you have learned the basic patterns of hormone Scientists wondered why tonic GnRH release occurred in secretion and gamete development, let’s look in detail at the pulses rather than in a steady fashion, but several studies have male and female reproductive systems. shown the signifi cance of the pulses. Children who suff er from a GnRH defi ciency will not mature sexually in the absence of gonadotropin stimulation of the gonads. If treated with steady infusions of GnRH through drug-delivery pumps, these chil- Concept Check Answers: End of chapter dren still fail to mature sexually. But if the pumps are adjusted to deliver GnRH in pulses similar to those that occur naturally, 9. What does aromatase do? the children will go through puberty. Apparently, steady high 10. What do the following abbreviations stand for? (Spelling counts!) FSH, levels of GnRH cause down-regulation of the GnRH receptors DHT, SRY, LH, GnRH, AMH on gonadotropin cells, making the pituitary unable to respond 11. Name the hypothalamic and anterior pituitary hormones that control to GnRH. reproduction. Th is receptor down-regulation is the basis for the therapeu- tic use of GnRH in treating certain disorders. For example, pa- tients with prostate and stimulated by androgens or estrogens may be given GnRH agonists to slow the growth Male Reproduction of the cells. It seems paradoxical to give these patients a drug that stimulates secretion of androgens and estrogens, but Th e consists of the testes, the in- aft er a brief increase in FSH and LH, the pituitary becomes in- ternal genitalia (accessory glands and ducts), and the exter- sensitive to GnRH. Th en FSH and LH secretion decreases, and nal genitalia. Th e external genitalia consist of the penis and gonadal output of steroid hormones also falls. In essence, the the scrotum , a saclike structure that contains the testes. Th e

910 Reproduction and Development

urethra serves as a common passageway for sperm and urine, urethra, its enlargement causes diffi culty in urinating by nar- although not simultaneously. It runs through the ventral as- rowing the passageway. pect of the shaft of the penis ( Fig. 26.7 a) and is surrounded Fetal development of the prostate gland, like that of the by a spongy column of tissue known as the corpus spongio- external genitalia, is under the control of dihydrotestosterone. sum { corpus, body; plural corpora}. Th e corpus spongiosum Discovery of the role of DHT in prostate growth led to the de- and two columns of tissue called the corpora cavernosa con- velopment of fi nasteride, a 5a -reductase inhibitor that blocks stitute the erectile tissue of the penis. DHT production. Th is drug was the fi rst nonsurgical treatment Th e tip of the penis is enlarged into a region called the for benign prostatic hypertrophy. glans that at birth is covered by a layer of skin called the fore- Th e Prostate Cancer Prevention Trial (PCPT) was a pla- skin, or prepuce. In some cultures, the foreskin is removed cebo-controlled study to see if finasteride could also prevent surgically in a procedure called circumcision. In the United prostate cancer. Nearly 19,000 men participated, with half of States, this practice goes through cycles of popularity. Propo- them receiving the drug and half receiving a placebo. Th e trial nents of the procedure claim that it is necessary for good hy- was stopped a year early aft er analysis of the results showed that giene, and they cite evidence suggesting that the incidence of the risk of developing prostate cancer fell by 25% in the men penile cancer, sexually transmitted diseases, and urinary tract taking the drug. infections is lower in circumcised men. Studies from Africa indicate that circumcising heterosexual adult men helps pre- vent infection with the HIV virus that causes AIDS (acquired Testes Produce Sperm and Hormones immunodeficiency syndrome). Opponents of circumcision The human testes are paired ovoid structures about 5 cm by claim that subjecting newborn boys to this surgical procedure 2.5 cm ( Fig. 26.7 a). Th e word testis means “witness” in Latin, but is unnecessary. the reason for its application to male reproductive organs is not Th e scrotum is an external sac into which the testes migrate clear. Testes are also called testicles . during fetal development. Th is location outside the abdominal Th e testes have a tough outer fi brous capsule that encloses cavity is necessary because normal sperm development requires masses of coiled seminiferous tubules clustered into 250–300 a temperature that is 2–3 °F lower than core body temperature. compartments (Fig. 26.7 c). Interstitial tissue consisting primar- Men who have borderline or low sperm counts are advised to ily of blood vessels and the testosterone-producing Leydig cells 26 switch from jockey-style underwear, which keeps the scrotum lies between the tubules (Fig. 26.7 e). Th e seminiferous tubules close to the body, to boxer shorts, which allow the testes to stay constitute nearly 80% of the testicular mass in an adult. Each in- cooler. dividual tubule is 0.3–1 meter long, and, if stretched out and laid The failure of one or both testes to descend is known as end to end, the entire mass would extend for about the length of cryptorchidism { crypto, hidden + orchis, testicle} and occurs in two and a half football fi elds. 1–3% of newborn males. If left alone, about 80% of cryptorchid Th e seminiferous tubules leave the testis and join the epi- testes spontaneously descend later. Th ose that remain in the ab- didymis { epi-, upon + didymos, twin}, a single duct that forms domen through puberty become sterile and are unable to pro- a tightly coiled cord on the surface of the testicular capsule (Fig. duce sperm. 26.7 c). Th e epididymis becomes the vas deferens { vas, vessel + Although cryptorchid testes lose their sperm-producing deferre, to carry away from}, also known as the ductus deferens . potential, they can produce androgens, indicating that hormone Th is duct passes into the abdomen, where it eventually empties production is not as temperature sensitive as sperm production. into the urethra, the passageway from the urinary bladder to the Because undescended testes are prone to become cancerous, au- external environment (see Fig. 26.7 a). thorities recommend that they be moved to the scrotum with testosterone treatment or, if necessary, surgically. Seminiferous Tubules The seminiferous tubules are the site Th e male accessory glands and ducts include the prostate of sperm production and contain two types of cells: spermato- gland, the seminal vesicles, and the bulbourethral (Cowper’s) gonia in various stages of becoming sperm and Sertoli cells glands (Fig. 26.7 b). Th e bulbourethral glands and seminal ves- (Fig. 26.7 d, e). Th e developing spermatocytes stack in columns icles empty their secretions into the urethra through ducts. Th e from the outer edge of the tubule to the lumen. Between each individual glands of the prostate open directly into the urethral column is a single Sertoli cell that extends from the outer edge lumen. of the tubule to the lumen. Surrounding the outside of the tu- Th e prostate gland is the best known of the three accessory bule is a basal lamina ( Fig. 26.7 e) that acts as a barrier, prevent- glands because of its medical signifi cance. Cancer of the prostate ing certain large molecules in the interstitial fl uid from entering is the most common form of cancer in men, and benign prostatic the tubule but allowing testosterone to enter easily. hypertrophy (enlargement) creates problems for many men af- Adjacent Sertoli cells in a tubule are linked to each other ter age 50. Because the prostate gland completely encircles the by tight junctions that form an additional barrier between the

911 Fig. 26.7 ANATOMY SUMMARY

The Male Reproductive System

(a) Reproductive anatomy of the male

Ureter

Urinary bladder

Prostate gland surrounds Seminal vesicle the urethra. Vas (ductus) deferens transports sperm from Urethra testes to urethra.

Bulbourethral gland Opening to ejaculatory duct

Corpus Dorsal spongiosum blood vessels Corpora cavernosa Corpora Penis cavernosa Central artery Glans

Prepuce Testis (foreskin) Corpus spongiosum

The scrotum holds the testes outside the abdominal cavity to keep them Urethra below body core temperature.

(b) Lateral view

Ureter Rectum

These accessory Urinary bladder glands contribute Pubic symphysis secretions to semen. (cartilage) Seminal vesicle Vas deferens Ejaculatory duct Prostate gland Bulbourethral gland Urethra

Penis

Epididymis

The testis is the site of sperm and hormone production. Scrotum

912 (c) Cutaway view of a testis showing coiled tubules (d) Cross section of a seminiferous tubule

Head of epididymis Capillary Sertoli cell Leydig cell

Lumen Seminiferous tubule Spermatogonium

Epididymis

Vas deferens

Scrotal cavity

(e) Sperm development Lumen of Luminal fluid composition is high seminiferous tubule + Mature sperm Spermatozoa in K and steroid hormones. Spermatids Sertoli cells secrete proteins to support sperm production. Secondary spermatocyte Tight junction between Sertoli cells Primary spermatocyte Fibroblast Germ cells Spermatogonium Basal lamina

Interstitial tissue

Capillary Leydig cells secrete testosterone.

(f) Semen is composed of sperm and (g) A sperm consists of a head with enzymes secretions from the accessory glands. and DNA, a long tail, and mitochondria.

COMPONENT FUNCTION SOURCE contains Sperm Gametes Seminiferous tubules Head enzymes to aid fertilization. Mucus Lubricant Bulbourethral glands Mid piece Water Provides liquid medium All accessory glands Nucleus

Buffers Neutralize acidic Prostate, bulbo- environment of vagina urethral glands

Nutrients Nourish sperm Centrioles Fructose Seminal vesicles Citric acid Prostate Vitamin C Seminal vesicles Mitochondrial Carnitine Epididymis spiral

Enzymes Clot semen in vagina, Seminal vesicles then liquefy the clot and prostate Microtubules

Zinc Unknown, possible Unknown Tail association with (flagellum)

Prostaglandins Smooth muscle Seminal vesicles FIGURE QUESTION contraction; may aid sperm transport What is the function of mitochondria in sperm?

913 Reproduction and Development

lumen of the tubule and the interstitial fluid outside the tu- HORMONAL CONTROL OF SPERMATOGENESIS bule. These tight junctions are sometimes called the blood- testis barrier because functionally they behave much like the impermeable capillaries of the blood-brain barrier, restricting movement of molecules between two compartments. Th e basal Hypothalamus – lamina and tight junctions create three compartments: the tu- GnRH bule lumen, a basal compartment on the basolateral side of the Sertoli cells, and the interstitial fl uid. Because of the barriers be- tween these compartments, the luminal fl uid has a composition diff erent from that of interstitial fl uid, with low concentrations Anterior + of glucose and high concentrations of K and steroid hormones. pituitary – – FSH LH Sertoli Cells Th e function of Sertoli cells is to regulate sperm development. Another name for Sertoli cells is sustentacular cells Leydig because they provide sustenance, or nourishment, for the de- cells veloping spermatogonia. Sertoli cells manufacture and secrete proteins that range from the hormones inhibin and activin to growth factors, enzymes, and androgen-binding protein (ABP). Testosterone (T) ABP is secreted into the seminiferous tubule lumen, where it binds to testosterone ( Fig. 26.8 ). Testosterone bound to pro- Spermatogonium To body tein is less lipophilic and cannot diff use out of the tubule lumen. Inhibin Spermatocyte for secondary effects Leydig Cells Leydig cells, located in the interstitial tissue be- tween seminiferous tubules (Fig. 26.7 d,e), secrete testoster- one. They first become active in the fetus, when testosterone Testes Second Sertoli is needed to direct development of male characteristics. Aft er messenger cell birth, the cells inactivate. At puberty they resume testosterone

production. Th e Leydig cells also convert some testosterone to Cell estradiol. Sertoli products cell Sperm Production Spermatogonia, the germ cells that un- dergo meiotic division to become sperm, are found clustered Androgen-binding near the basal ends of the Sertoli cells, just inside the basal protein (ABP) ABP T lamina of the seminiferous tubules ( Fig. 26.7 d,e). In this basal compartment, they undergo mitosis to create additional germ cells. Some of the spermatogonia remain here to produce future Fig. 26.8 spermatogonia. Other spermatogonia start meiosis and become primary spermatocytes. fertilization. Mitochondria to produce energy for sperm move- As spermatocytes diff erentiate into sperm, they move in- ment concentrate in the midpiece of the sperm body, along with ward toward the tubule lumen, continuously surrounded by microtubules that extend into the tail. Th e result is a small, mo- Sertoli cells. Th e tight junctions of the blood-testis barrier break tile gamete that bears little resemblance to the parent spermatid. and reform around the migrating cells, ensuring that the bar- Sperm are released into the lumen of the seminiferous tu- rier remains intact. By the time spermatocytes reach the luminal bule, along with secreted fl uid. From there, they are free to move ends of Sertoli cells, they have divided twice and become sper- out of the testis. Th e entire development process—from sper- matids ( Fig. 26.5 ). matogonium division until sperm release—takes about 64 days. Spermatids remain embedded in the apical membrane of At any given time, diff erent regions of the tubule contain sper- Sertoli cells while they complete the transformation into sperm, matocytes in diff erent stages of development. Th e staggering of losing most of their cytoplasm and developing a fl agellated tail developmental stages allows sperm production to remain nearly (Fig. 26.7 g). The chromatin of the nucleus condenses into a constant at a rate of 200 million sperm per day. Th at may sound dense structure that fi lls most of the head, while a lysosome-like like an extraordinarily high number, but it is about the number vesicle called an acrosome fl attens out to form a cap over the of sperm released in a single ejaculation. tip of the nucleus. Th e acrosome contains enzymes essential for

914 Reproduction and Development

Sperm just released from Sertoli cells are not yet mature synthesis of paracrine molecules needed for spermatogonia mi- and are incapable of swimming. Th ey are pushed out of the tu- tosis and spermatogenesis. In addition, FSH stimulates produc- bule lumen by other sperm and by bulk fl ow of the fl uid secreted tion of androgen-binding protein and inhibin. by Sertoli cells. Sperm entering the epididymis complete their Th e primary target of LH is the Leydig cells, which pro- maturation during the 12 or so days of their transit time, aided duce testosterone. In turn, testosterone feeds back to inhibit LH by protein secretions from epididymal cells. and GnRH release. Testosterone is essential for spermatogen- esis, but its actions appear to be mediated by Sertoli cells, which have androgen receptors. Spermatocytes lack androgen recep- Spermatogenesis Requires Gonadotropins tors and cannot respond directly to testosterone. and Testosterone Spermatogenesis is a very diffi cult process to study in vivo Th e hormonal control of spermatogenesis follows the general or in vitro, and the available animal models may not accurately pattern described previously: hypothalamic GnRH promotes reflect the situation in the human testis. For these reasons, it release of LH and FSH from the anterior pituitary (Fig. 26.8 ). may be some time before we can say with certainty how testos- FSH and LH in turn stimulate the testes. The gonadotropins terone and FSH regulate spermatogenesis. were named originally for their eff ect on the female ovary, but the same names have been retained in the male. Concept Check Answers: End of chapter GnRH release is pulsatile, peaking every 1.5 hours, and LH release follows the same pattern. FSH levels are not as obviously 12. What do Sertoli cells secrete? What do Leydig cells secrete? related to GnRH secretion because FSH secretion is also infl u- 13. Because GnRH agonists cause down-regulation of GnRH receptors, enced by inhibin and activin. what would be the advantages and disadvantages of using these drugs FSH targets Sertoli cells. Unlike oocytes, male germ cells as a male contraceptive? do not have FSH receptors. Instead, FSH stimulates Sertoli 14. Name another important lipophilic molecule that binds to protein to make it more soluble in body fl uid.

RUNNING PROBLEM 26 Male Accessory Glands Contribute Infertility can be caused by problems in either the man or the . Sometimes, however, both partners have Secretions to Semen problems that contribute to their infertility. In general, male Th e male reproductive tract has three accessory glands—bulbo- infertility is caused by low sperm counts, abnormalities in urethral glands, seminal vesicles, and prostate—whose primary sperm morphology, or abnormalities in the reproductive function is to secrete various fl uid mixtures (Fig. 26.7 b). When structures that carry sperm. Female infertility may be caused sperm leave the vas deferens during ejaculation, they are joined by problems in hormonal pathways that govern maturation by these secretions, resulting in a sperm-fl uid mixture known as and release of eggs or by abnormalities of the reproductive semen. About 99% of the volume of semen is fl uid added from structures (cervix, uterus, ovaries, oviducts). Because tests the accessory glands. of male fertility are simple to perform, Dr. Coddington fi rst analyzes Larry’s sperm. In this test, trained technicians Accessory gland contributions to the composition of se- examine a fresh sperm sample under a microscope. They men are listed in Figure 26.7 f. Semen provides a liquid medium note the shape and motility of the sperm and estimate the for delivering sperm. Th e bulbourethral glands contribute mu- concentration of sperm in the sample. cus for lubrication and buff ers to neutralize the usually acidic environment of the vagina. Seminal vesicles contribute prosta- Q1: Name (in order) the male reproductive structures that glandins that appear to infl uence sperm motility and transport carry sperm from the testes to the external environment. in both male and female reproductive tracts. Prostaglandins Q2: A new technique for the treatment of male infertility were originally believed to come from the prostate gland, and involves retrieval of sperm from the epididymis. The the name was well established by the time their true source was retrieved sperm can be used to fertilize an egg, which discovered. Both the prostate and seminal vesicles contribute is then implanted in the uterus. Which causes of male nutrients for sperm metabolism. infertility might make this treatment necessary? In addition to providing a medium for sperm, accessory gland secretions help protect the male reproductive tract from pathogens that might ascend the urethra from the external en- vironment. Th e secretions physically fl ush out the urethra and supply immunoglobulins, lysozyme, and other compounds with

915 Reproduction and Development

antibacterial action. One interesting component of semen is Females Have an Internal Uterus zinc. Its role in reproduction is unclear, but concentrations of zinc below a certain level are associated with male infertility. Th e female external genitalia are known collectively as either the vulva or the pudendum { vulva, womb; pudere, to be ashamed}. They are shown in Figure 26.9 c , the view seen by a healthcare Androgens Infl uence Secondary worker who is about to do a pelvic exam or take a Pap smear. Sex Characteristics Starting at the periphery are the labia majora { labium, lip}, folds of skin that arise from the same embryonic tissue as the scro- Androgens have a number of eff ects on the body in addition tum. Within the labia majora are the labia minora, derived from to gametogenesis. Th ese eff ects are divided into primary and embryonic tissues that in the male give rise to the shaft of the pe- secondary sex characteristics. Primary sex characteristics are nis (see Fig. 26.2 b). Th e clitoris is a small bud of erectile, sensory the internal sexual organs and external genitalia that distin- tissue at the anterior end of the vulva, enclosed by the labia mi- guish males from females. As you have already learned, andro- nora and an additional fold of tissue equivalent to the foreskin of gens are responsible for the diff erentiation of male genitalia the penis. during embryonic development and for their growth during In females, the urethra opens to the external environment puberty. between the clitoris and the vagina {vagina, sheath}, the cavity The secondary sex characteristics are other traits that that acts as receptacle for the penis during intercourse. At birth, distinguish males from females. Th e male body shape is some- the external opening of the vagina is partially closed by a thin ring times described as an inverted triangle, with broad shoulders of tissue called the hymen, or maidenhead . Th e hymen is external and narrow waist and hips. Th e female body is usually more to the vagina, not within it, so the normal use of tampons dur- pear shaped, with broad hips and narrow shoulders. Andro- ing will not rupture the hymen. However, it can be gens are responsible for such typically male traits as beard and stretched by normal activities such as cycling and horseback riding body hair growth, muscular development, thickening of the and therefore is not an accurate indicator of a woman’s virginity. vocal chords with subsequent lowering of the voice, and be- Now let’s follow the path of sperm deposited in the vagina havioral eff ects, such as the sex drive, also called libido { libido , during intercourse. To continue into the female reproductive desire, lust]. tract, sperm must pass through the narrow opening of the cer- Androgens are anabolic hormones that promote pro- vix, the neck of the uterus that protrudes slightly into the upper tein synthesis, which gives them their street name of anabolic end of the vagina ( Fig. 26.9 a). Th e cervical canal is lined with steroids . The illicit use of these drugs by athletes has been mucous glands whose secretions create a barrier between the widespread despite possible adverse side eff ects such as liver vagina and uterus. tumors, infertility, and excessive aggression ( ‘roid rage). One of Sperm that make it through the cervical canal arrive in the the more interesting side eff ects is the apparent addictiveness lumen of the uterus, or womb, a hollow, muscular organ slightly of anabolic steroids. Withdrawal from the drugs may be associ- smaller than a woman’s clenched fi st. Th e uterus is the structure ated with behavioral changes that include depression, psycho- in which fertilized eggs implant and develop during pregnancy. sis, or aggression. Th ese psychiatric disturbances suggest that It is composed of three tissue layers ( Fig. 26.9 d): a thin outer human brain function can be modulated by sex steroids, just connective tissue covering, a thick middle layer of smooth mus- as the brain function of other animals can. Fortunately, many cle known as the myometrium, and an inner layer known as the side eff ects of anabolic steroids are reversible once their use is endometrium { metra, womb}. discontinued. The endometrium consists of an epithelium with glands that dip into a connective tissue layer below. Th e thickness and character of the endometrium vary during the menstrual cycle. Answers: End of chapter Concept Check Cells of the epithelial lining alternately proliferate and slough 15. Explain why the use of exogenous anabolic steroids might shrink a off , accompanied by a small amount of bleeding in the process man’s testes and make him temporarily infertile. known as menstruation { menstruus, monthly}. Sperm swimming upward through the uterus leave its cav- ity through openings into the two fallopian tubes (Fig. 26.9 a). Th e fallopian tubes are 20–25 cm long and about the diameter of Female Reproduction a drinking straw. Th eir walls have two layers of smooth muscle, Female reproduction is an example of a physiological pro- longitudinal and circular, similar to the walls of the intestine. A cess that is cyclic rather than steady state. Th e cycles of gamete ciliated epithelium lines the inside of the tubes. production in the ovary and the interactions of reproductive Fluid movement created by the cilia and aided by muscular hormones and feedback pathways are part of one of the most contractions transports an egg along the fallopian tube toward complex control systems of the human body.

916 Reproduction and Development the uterus. If sperm moving up the tube encounter an egg mov- The corpus luteum secretes hormones that continue the ing down the tube, fertilization may occur. Pathological con- preparations for pregnancy. If a pregnancy does not oc- ditions in which ciliary function is absent are associated with cur, the corpus luteum ceases to function aft er about two female infertility and with in which the embryo im- weeks, and the ovarian cycle begins again. plants in the fallopian tube rather than the uterus. Th e endometrial lining of the uterus also goes through a The flared open end of the fallopian tube divides into cycle—the uterine cycle—regulated by ovarian hormones: fingerlike projections called fimbriae {fimbriae, fringe}. The fi mbriae (Fig. 26.9 a) are held close to the adjacent ovary by con- 1 Menses. Th e beginning of the in the ovary nective tissue, which helps ensure that eggs released from the corresponds to menstrual bleeding from the uterus. surface of the ovary will be swept into the tube rather than fl oat- 2 Proliferative phase. Th e latter part of the ovary’s follicular ing off into the abdominal cavity. phase corresponds to the proliferative phase in the uterus, during which the endometrium adds a new layer of cells in anticipation of pregnancy. The Ovary Produces Eggs and Hormones 3 Secretory phase. A ft er ovulation, hormones from the cor- The ovary is an elliptical structure, about 2–4 cm long pus luteum convert the thickened endometrium into a se- (Fig. 26.9 e). It has an outer connective tissue layer and an in- cretory structure. Th is means that the of the ner connective tissue framework known as the stroma {stroma, ovarian cycle corresponds to the secretory phase of the mattress}. Most of the ovary consists of a thick outer cortex uterine cycle. If no pregnancy occurs, the superfi cial layers fi lled with ovarian follicles in various stages of development or of the secretory endometrium are lost during menstrua- decline. Th e small central medulla contains nerves and blood tion as the uterine cycle begins again. vessels. Th e ovary, like the testis, produces both gametes and hor- mones. As mentioned earlier, about 7 million oögonia in the Hormonal Control of the Menstrual embryonic ovary develop into half a million primary oocytes. Cycle Is Complex Each primary oocyte is enclosed in a primary follicle with a single layer of granulosa cells separated by a basement mem- Th e ovarian and uterine cycles are under the primary control of 26 brane from an outer layer of cells known as the theca { theke, various hormones: case or cover}. • GnRH from the hypothalamus • FSH and LH from the anterior pituitary A Menstrual Cycle Lasts about One Month • Estrogen, progesterone, inhibin, and AMH from the ovary During the follicular phase, the dominant steroid hor- Female humans produce gametes in monthly cycles (average mone is estrogen ( Fig. 26.10 ). Ovulation is triggered by surges 28 days; normal range 24–35 days). Th ese cycles are commonly in LH and FSH. In the luteal phase, progesterone is dominant, called menstrual cycles because they are marked by a 3–7 day although estrogen is still present. period of bloody uterine discharge known as the menses { men- Anti-Müllerian hormone (AMH) was fi rst known for its ses, months}, or menstruation . Th e menstrual cycle can be de- role in male development, but scientists have discovered that scribed by following changes that occur in follicles of the ovary, AMH is also produced by ovarian follicles in the fi rst part of the the ovarian cycle, or by following changes in the endometrial ovarian cycle. AMH apparently acts as a brake to keep too many lining of the uterus, the uterine cycle. Figure 26.10 is a sum- follicles from developing at one time. mary fi gure showing a typical menstrual cycle and its phases. Now let’s go through an ovarian cycle in detail. Notice that the ovarian cycle is divided into three phases: 1 Follicular phase. Th e fi rst part of the ovarian cycle, known Early Follicular Phase Th e fi rst day of menstruation is day 1 as the follicular phase, is a period of follicular growth in of a cycle. Th is point was chosen to start the cycle because the the ovary. This phase is the most variable in length and bleeding of menstruation is an easily observed physical sign. lasts from 10 days to 3 weeks. Just before the beginning of each cycle, gonadotropin secretion 2 Ovulation. Once one or more follicles have ripened, the from the anterior pituitary increases. Under the influence of ovary releases the oocyte(s) during ovulation . FSH, several follicles in the ovaries begin to mature (second row 3 Luteal phase. The phase of the ovarian cycle following of Fig. 26.10 and Fig. 26.11 ). ovulation is known as the postovulatory or luteal phase . As the follicles grow, their granulosa cells (under the infl u- Th e second name comes from the transformation of a rup- ence of FSH) and their thecal cells (under the infl uence of LH) tured follicle into a corpus luteum {corpus, body + luteus , start to produce steroid hormones ( Fig. 26.12 ). Granulosa yellow}, named for its yellow pigment and lipid deposits. cells also begin to secrete AMH. Th is AMH decreases follicle

917 Fig. 26.9 ANATOMY SUMMARY

The Female Reproductive System

(a) Internal reproductive structures

Uterine Fallopian Ovary cavity tube

Fimbriae

Mammary glands

Uterus

Cervical canal

Cervix

Vagina

(b) Cross-sectional view of pelvis

Ovary Fallopian tube

Uterus

Urinary bladder Cervix Pubic symphysis Rectum Urethra Vagina

Clitoris

Labium Labium Anus minus majus

918 (c) Female external genitalia

This is the view seen by a healthcare provider doing a pelvic exam.

Clitoris

Urethral opening Labium minus

Labium majus Vagina

Hymen (stretched)

Anus

26

(d) Structure of the uterus

Endometrium is glandular Myometrium Outer epithelium whose structure is smooth connective (e) Cross section of an ovary, showing all varies with phases of the muscle. tissue different stages of follicular development. menstrual cycle.

Secondary follicle Primary Oocyte follicles Uterine Mature cavity follicle

Uterine artery Stroma Ruptured follicle

Artery Vein

Ovulated Corpus Regressing oocyte luteum corpus luteum

919 Reproduction and Development

THE MENSTRUAL CYCLE

This 28-day menstrual cycle is divided into phases based on events in the ovary (ovarian cycle) and in the uterus (uterine cycle).

PHASES OF THE OVARIAN CYCLE FOLLICULAR PHASE OVULATION LUTEAL PHASE

Gonadotrophic LH hormone levels

FSH

Ovarian cycle

Primary Corpus Mature Corpus follicle Theca Antrum Ovulation luteum corpus albicans formation luteum

Ovarian hormone Progesterone levels

Estrogen Inhibin

Uterine cycle

PHASES OF THE PROLIFERATIVE MENSES SECRETORY PHASE UTERINE CYCLE PHASE

Basal body 36.7 temperature (°C) 36.4

DAYS 28/0 7142128/0 Fig. 26.10

920 Reproduction and Development

FOLLICULAR DEVELOPMENT

Surface epithelium Theca Basal lamina Granulosa cells Antral fluid

Antrum

Primary Secondary Tertiary Ovulation Corpus luteum Corpus follicle follicle follicle formation albicans

OVARIAN BEFORE FSH EARLY FOLLICULAR LATE FOLLICULAR LUTEAL POST-LUTEAL PHASE STIMULATION PHASE PHASE PHASE PHASE

Follicle stage Primary follicle Secondary follicle Tertiary follicle Corpus luteum Corpus albicans

Ovum Primary oocyte Primary oocyte Becomes secondary oocyte None None with division arrested

Zona pellucida* Minimal Increased in width Present None None

Granulosa cells Single layer 2–6 cell layer 3–4 cell layer Converted to Cells degenerate luteal cells Antrum None None Develops within granulosa Fills with None 26 layer and fills with fluid; migrating cells swells to 15–20 mm in diameter

Basal lamina Separates Present Present Disappears None granulosa and theca

Theca Single cell layer Single cell layer Inner layer: secretory and Converted to Cells degenerate plus blood small blood vessels luteal cells vessels Outer layer: connective tissue, smooth muscle cells, large blood vessels

*The is a glycoprotein coat that protects the ovum. Fig. 26.11 sensitivity to FSH, which apparently prevents recruitment of ad- by the granulosa cells. Th is positive feedback loop allows the fol- ditional primary follicles once one group has started developing. licles to continue estrogen production even though FSH and LH Physicians now use blood AMH levels as an indicator of how levels decrease. many follicles are developing early in a cycle and as a marker In the uterus, menstruation ends during the early follicular for the condition known as polycystic ovary syndrome (PCOS) , phase (Fig 26.10). Under the infl uence of estrogen from devel- in which ovarian follicles form fl uid-fi lled cysts. oping follicles, the endometrium begins to grow, or proliferate. Thecal cells synthesize androgens that diffuse into the Th is period is characterized by an increase in cell number and neighboring granulosa cells, where aromatase converts them by enhanced blood supply to bring nutrients and oxygen to the to estrogens ( Fig. 26.12 a). Gradually increasing estrogen levels thickening endometrium. Estrogen also causes mucous glands in the circulation have several eff ects. Estrogen exerts negative of the cervix to produce clear, watery mucus. feedback on pituitary FSH and LH secretion, which prevents the development of additional follicles in the same cycle. At the Mid to Late Follicular Phase As the follicles enlarge, granu- same time, estrogen stimulates additional estrogen production losa cells begin to secrete fl uid that collects in a central cavity in

921 Reproduction and Development

HORMONAL CONTROL OF THE MENSTRUAL CYCLE

LH FSH

Ovum

Follicle Corpus luteum Estrogen Inhibin Progesterone

(a) Early to mid-follicular phase (b) Late follicular phase and ovulation (c) Early to mid-luteal phase (d) Late luteal phase Low levels of estrogen exert negative Rising levels of estrogen plus Combined estrogen Estrogen and progesterone feedback to GnRH, FSH, LH. Estrogen increasing progesterone cause and progesterone fall when corpus luteum dies. promotes more estrogen secretion by the LH surge. FSH is suppressed shut off FSH and LH. Gonadotropins start follicular the follicle. AMH prevents more by inhibin. development for a new cycle. follicles from developing.

– + + – GnRH GnRH GnRH GnRH

Pituitary Hypothalamus – Tonic secretion resumes

– + – – FSH LH FSH LH FSH LH FSH LH

Corpus luteum Corpus Follicle (from ovulated New follicles luteum Follicle follicle) begin to dies + Granulosa Thecal develop Granulosa Thecal cells cells secretes cells cells

Estrogen Inhibin Androgens Progesterone Estrogen and AMH Androgens Inhibin progesterone Estrogens High estrogen Small amount of output progesterone

Fig. 26.12

the follicle known as the antrum {antron, cave} (Fig. 26.11 ). An- follicle is still developing. As the follicular phase ends, granulosa tral fl uid contains hormones and enzymes needed for ovulation. cells of the dominant follicle begin to secrete inhibin and pro- At each stage of follicular development, some follicles undergo gesterone in addition to estrogen. Estrogen, which had exerted a atresia (hormonally regulated cell death). Only a few follicles negative feedback eff ect on GnRH earlier in the follicular phase, reach the fi nal stage, and usually only one dominant follicle de- changes to positive feedback, leading to a preovulatory GnRH velops until ovulation. surge. As the follicular phase nears its end, ovarian estrogen se- Immediately before ovulation, the persistently high lev- cretion peaks ( Fig. 26.12 b). By this point of the cycle, only one els of estrogen, aided by rising levels of progesterone, enhance

922 Reproduction and Development

pituitary responsiveness to GnRH. As a result, LH secretion RUNNING PROBLEM increases dramatically, a phenomenon known as the LH surge . FSH surges also, but to a lesser degree, presumably because it is The results of Larry’s sperm analysis are normal. Dr. Coddington being suppressed by inhibin and estrogen. is therefore able to rule out sperm abnormalities as a cause Th e LH surge is an essential part of ovulation. Without it, of Peggy and Larry’s infertility. Peggy is instructed to take her the fi nal steps of oocyte maturation cannot take place. Meiosis body temperature daily and record the results on a chart. This resumes in the developing follicle with the first meiotic divi- temperature tracking is intended to determine whether or not sion, which converts the primary oocyte into a secondary oo- she is ovulating. Following ovulation, body temperature rises cyte (egg) and a polar body, which is extruded ( Fig. 26.5 ). While slightly and remains elevated through the remainder of the this division is taking place, antral fl uid collects and the follicle menstrual cycle. grows to its greatest size, preparing to release the egg. Q3: For which causes of female infertility is temperature High levels of estrogen in the late follicular phase prepare tracking useful? For which causes is it not useful? the uterus for a possible pregnancy. Th e endometrium grows to a thickness of 3–4 mm ( Fig. 26.10 ). Just before ovulation, the cervical glands produce copious amounts of thin, stringy mucus to facilitate sperm entry. Th e stage is set for ovulation. will provide nourishment for a developing embryo while the placenta, the fetal-maternal connection, is developing. Ovulation About 16–24 hours aft er LH peaks, ovulation oc- Progesterone also causes cervical mucus to thicken. curs (Fig. 26.10 ). The mature follicle secretes collagenase, an Th icker mucus creates a plug that blocks the cervical opening, enzyme that dissolves collagen in the connective tissue holding preventing bacteria as well as sperm from entering the uterus. the follicular cells together. Th e breakdown products of colla- One interesting eff ect of progesterone is its thermogenic gen create an infl ammatory reaction, attracting leukocytes that ability. During the luteal phase of an ovulatory cycle, a wom- secrete prostaglandins into the follicle. Th e prostaglandins may an’s basal body temperature, taken immediately upon awaken- cause smooth muscle cells in the outer theca to contract, ruptur- ing and before getting out of bed, jumps 0.3–0.5 °F and remains ing the follicle wall at its weakest point. Antral fl uid spurts out elevated until menstruation. Because this change in the tem- along with the egg, which is surrounded by two to three layers of perature setpoint occurs aft er ovulation, it cannot be used eff ec- 26 granulosa cells. Th e egg is swept into the fallopian tube and car- tively to predict ovulation. However, it is a simple way to assess ried away to be fertilized or to die. whether a woman is having ovulatory or anovulatory (non- In addition to promoting follicular rupture, the LH surge ovulating) cycles. causes follicular thecal cells to migrate into the antral space, mingling with the former granulosa cells and fi lling the cavity. Late Luteal Phase and Menstruation Th e corpus luteum has Both cell types then transform into luteal cells of the corpus lu- an intrinsic life span of approximately 12 days. If pregnancy teum. Th is process, known as luteinization, involves biochemi- does not occur, the corpus luteum spontaneously undergoes cal and morphological changes. apoptosis to become an inactive structure called a corpus albi- cans {albus, white}. As the luteal cells degenerate, progesterone Early to Mid-Luteal Phase After ovulation, newly formed and estrogen production decrease (Fig. 26.12 d). This fall re- luteal cells accumulate lipid droplets and glycogen granules in moves the negative feedback signal to the pituitary and hypo- their cytoplasm and begin to secrete progesterone. Estrogen thalamus, so secretion of FSH and LH increases. synthesis diminishes initially but as the luteal phase progresses, Maintenance of a secretory endometrium depends on the the corpus luteum produces steadily increasing amounts of pro- presence of progesterone. When the corpus luteum degener- gesterone and estrogen. Progesterone is the dominant hormone ates and hormone production decreases, blood vessels in the of the luteal phase. Estrogen levels increase but never reach the surface layer of the endometrium contract. Without oxygen and peak seen before ovulation. nutrients, the surface cells die. About two days aft er the corpus Th e combination of estrogen and progesterone exerts neg- luteum ceases to function, or 14 days aft er ovulation, the endo- ative feedback on the hypothalamus and anterior pituitary ( Fig. metrium begins to slough its surface layer, and menstruation 26.12 c). Gonadotropin secretion, further suppressed by luteal begins. inhibin production, remains shut down throughout most of the Menstrual discharge from the uterus totals about 40 luteal phase. mL of blood and 35 mL of serous fluid and cellular debris. Under the influence of progesterone, the endometrium There are usually few clots of blood in the menstrual flow continues its preparation for pregnancy and becomes a secre- because of the presence of plasmin, which breaks up clots. tory structure. Endometrial glands coil, and additional blood vessels grow into the connective tissue layer. Endometrial cells deposit lipids and glycogen in their cytoplasm. Th ese deposits

923 Reproduction and Development

Menstruation continues for 3–7 days, well into the follicular Human sexual response in both sexes is divided into four phase of the next ovulatory cycle. phases: (1) excitement, (2) plateau, (3) , and (4) resolu- tion. In the excitement phase, various erotic stimuli prepare the genitalia for the act of copulation. For the male, excitement in- Hormones Infl uence Female Secondary volves erection of the penis. For the female, it includes erection Sex Characteristics of the clitoris and vaginal lubrication. In both sexes, erection is a Estrogens control the development of primary sex characteristics state of vasocongestion in which arterial blood fl ow into spongy in females, just as androgens control them in males. Estrogens erectile tissue exceeds venous outfl ow. also control the most prominent female secondary sex traits: Erotic stimuli include sexually arousing tactile stimuli as and the female pattern of fat distribution well as psychological stimuli. Because the latter vary widely (hips and upper thighs). Other female secondary sex charac- among individuals and among cultures, what is erotic to one teristics, however, are governed by androgens produced in the person or in one culture may be considered disgusting by an- adrenal cortex. Pubic and axillary (armpit) hair growth and other individual or in another culture. Regions of the body that possess receptors for sexually arousing tactile stimuli are called libido (sex drive) are under the control of adrenal androgens. erogenous zones and include the genitalia as well as the lips, tongue, nipples, and ear lobes. Concept Check Answers: End of chapter In the plateau phase, changes that started during excite- 16. Name the phases of the ovarian cycle and the corresponding phases of ment intensify and peak in an orgasm (climax). In both sexes, the uterine cycle. orgasm is a series of muscular contractions accompanied by in- tense pleasurable sensations and increased blood pressure, heart 17. What side eff ects would you predict in female athletes who take rate, and respiration rate. In females, the uterus and walls of the anabolic steroids to build muscles? vagina contract. In males, the contractions usually result in the 18. Aromatase converts testosterone to estrogen. What would happen to ejaculation of semen from the penis. Female orgasm is not re- the ovarian cycle of a woman given an aromatase inhibitor? quired for pregnancy. 19. On what day of the menstrual cycle will a woman with the following Th e fi nal phase of the sexual response is resolution, a pe- cycle lengths ovulate? riod during which the physiological parameters that changed in (a) 28 days (b) 23 days (c) 31 days the fi rst three phases slowly return to normal. The Male Sex Act Includes Erection Procreation and Ejaculation Reproduction throughout the animal kingdom is marked by A key element to successful copulation is the ability of the male species-specific behaviors designed to ensure that egg and to achieve and sustain an erection. Sexual excitement from ei- sperm meet. For aquatic animals that release gametes into the ther tactile or psychological stimuli triggers the erection refl ex, water, coordinated timing is everything. Interaction between males and females of these species may be limited to chemical RUNNING PROBLEM communication by pheromones. In terrestrial vertebrates, internal fertilization requires inter- Results of the temperature tracking for several months active behaviors and specialized adaptations of the genitalia. For reveal that Peggy is ovulating regularly. Dr. Coddington example, the female must have an internal receptacle for sperm therefore believes that her ovaries are functioning normally. (the vagina in humans), and the male must possess an organ (the Other possible causes for this couple’s infertility include penis in humans) that can place sperm in the receptacle. Th e hu- abnormalities in Peggy’s cervix, fallopian tubes, or uterus. man penis is fl accid (soft and limp) in its resting state, not capable Dr. Coddington next decides to order a postcoital test. In this of penetrating the narrow opening of the vagina. In the male sex test, the couple is instructed to have intercourse 12 hours act, the penis fi rst stiff ens and enlarges during erection, and then before the physician visit. Cervical mucus is then analyzed. releases sperm from the ducts of the reproductive tract during This test will also analyze the interaction between sperm and mucus. ejaculation . Without these events, fertilization cannot take place. Q4: What abnormalities in the cervix, fallopian tubes, and The Human Sexual Response Has Four Phases uterus could cause infertility? Th e human sex act—also known as , copula- tion, or coitus { coitio, a coming together}—is highly variable in some ways and highly stereotypical in other ways.

924 Reproduction and Development a spinal refl ex that is subject to control from higher centers in vas deferens and into the urethra, where they are joined by se- the brain. Th e urination and defecation refl exes are similar types cretions from the accessory glands to make semen. Th e average of refl exes. semen volume is 3 mL (range 2–6 mL), of which less than 10% In its simplest form, the erection refl ex begins with tactile is sperm. stimuli sensed by mechanoreceptors in the glans penis or other During ejaculation, semen in the urethra is expelled to the erogenous zones ( Fig. 26.13 ). Sensory neurons signal the spi- exterior by a series of rapid muscular contractions accompanied nal integration center, which inhibits vasoconstrictive sympa- by sensations of intense pleasure—the orgasm. A sphincter at thetic input on penile arterioles. Simultaneously, nitric oxide the base of the bladder contracts to prevent sperm from enter- produced by increased parasympathetic input actively dilates ing the bladder and urine from joining the semen. the penile arterioles. As arterial blood fl ows into the open spaces Both erection and ejaculation can occur in the absence of the erectile tissue, it passively compresses the veins and traps of mechanical stimulation. Sexually arousing thoughts, sights, blood. The erectile tissue becomes engorged, stiffening and sounds, emotions, and dreams can all initiate and lengthening the penis within 5–10 seconds. even lead to orgasm in both men and women. In addition, non- Th e climax of the male sexual act coincides with emission sexual penile erection accompanies rapid eye movement (REM) and ejaculation. Emission is the movement of sperm out of the sleep.

THE ERECTION REFLEX

Erection can take place without input from higher brain centers. It can also be stimulated (and inhibited) by descending pathways Thoughts from the cerebral cortex. Spontaneous occur during about REM sleep. sex!!

KEY

Stimulus 26 Sensor Erotic Higher brain Afferent pathway stimuli centers

Integrating center

Output signal

Target Descending autonomic Ascending sensory Tissue response pathways pathway

+

Parasympathetic stimulated

Sympathetic – Penile arterioles inhibited vasodilate.

Penis Spinal Erection cord

Tactile Sensory stimuli neuron

Mechanoreceptor

Fig. 26.13

925 Reproduction and Development

Sexual Dysfunction Aff ects Males and Females without using any form of will get pregnant within a year. Many women, however, get pregnant aft er just a Th e inability to achieve or sustain a penile erection is known as single unprotected encounter. Couples who hope to avoid un- erectile dysfunction (ED) or impotence . Erectile dysfunction is a wanted pregnancies generally use some form of birth control, or matter of global concern because inability to achieve and sustain contraception. an erection disrupts the sex act for both men and women. Organic Contraceptive practices fall into several broad groups. (physiological and anatomical) causes of ED include neural and Abstinence, the total avoidance of sexual intercourse, is the sur- hormonal problems, vascular insuffi ciency, and drug-induced ED. est method to avoid pregnancy (and sexually transmitted dis- A variety of psychological causes can also contribute to ED. eases). Some couples practice abstinence only during times of Alcohol inhibits sexual performance in both men and suspected fertility calculated using fertility-awareness methods women, as noted by Shakespeare in Macbeth (II, iii). When of birth control. Macduff asks, “What three things does drink especially pro- Sterilization is the most effective contraceptive method voke?” the porter answers, “Marry, sir, nose-painting, sleep, and for sexually active people, but it is a surgical procedure and is urine. Lechery, sir, it provokes and unprovokes: it provokes the not easily reversed. Female sterilization is called tubal ligation . desire, but it takes away the performance.” Several antidepres- It consists of tying off and cutting the fallopian tubes. A woman sant drugs list loss of libido among their side eff ects. with a tubal ligation still ovulates, but the eggs remain in the Erectile dysfunction in men over age 40 is now considered abdomen. Th e male form of sterilization is the vasectomy, in a marker for cardiovascular disease and atherosclerosis, and which the vas deferens is tied and clipped. Sperm are still made sometimes ED is the fi rst clinical sign of these conditions. Erec- in the seminiferous tubules, but because they cannot leave the tions occur when neurotransmitters from pelvic nerves increase reproductive tract, they are reabsorbed. endothelial production of nitric oxide (NO), which increases Interventional methods of contraception include (1) barrier cGMP and results in vasodilation of penile arterioles. Endothe- methods, which prevent union of eggs and sperm; (2) methods lial dysfunction and failure to produce adequate NO occur in that prevent implantation of the fertilized egg; and (3) hormonal atherosclerosis and diabetes mellitus, making ED an early mani- treatments that decrease or stop gamete production. The ef- festation of vascular pathology. fi cacy of interventional contraceptives depends in part on how In 1998 the U.S. Food and Drug Administration (FDA) ap- consistently and correctly they are used ( Tbl. 26.1 ). proved sildenafi l (Viagra ® ) for the treatment of erectile dysfunc- tion. Sildenafi l and similar drugs in the same class prolong the Barrier Methods Contraceptive methods based on chemical eff ects of nitric oxide by blocking phosphodiesterase-5 (PDE-5), or physical barriers are among the earliest recorded means of the enzyme that degrades cGMP. Clinical trials have shown that birth control. Once people made the association between preg- phosphodiesterase inhibitors are very eff ective in correcting ED nancy and semen, they concocted a variety of physical barriers but are not without side eff ects. Th e U.S. Federal Aviation Ad- and spermicides {cida , killer} to kill sperm. An ancient Egyptian ministration issued an order that pilots should not take sildena- papyrus with the earliest known references to birth control de- fi l within six hours of fl ying because 3% of men report impaired scribes the use of vaginal plugs made of leaves, feathers, figs, color vision (a blue or greenish haze). Th is impairment occurs and alum held together with crocodile and elephant dung. Sea because sildenafi l also inhibits an enzyme in the retina. sponges soaked in vinegar and disks of oiled silk have also been When the FDA approved PDE-5 inhibitors for male erec- used at one time or another. In subsequent centuries women tile dysfunction, women wondered if the drug, which promotes used douches of garlic, turpentine, and rose petals to rinse the the erection reflex, would improve their sexual response. Al- vagina after intercourse. As you can imagine, many of these though women do have clitoral erections, the female sexual re- methods also caused vaginal or uterine infections. sponse is more complicated. Studies on the effi cacy of PDE-5 Modern versions of the female barrier include the dia- inhibitors for orgasmic dysfunction in women have had mixed phragm, introduced into the United States in 1916. Th ese rub- results. Instead, pharmaceutical companies are testing other ber domes and a smaller version called a cervical cap are usually drugs for female sexual dysfunction. Th e most promising can- filled with a spermicidal cream, then inserted into the top of didates, now in late clinical trials, are based on testosterone, the the vagina so they cover the cervix. One advantage to the dia- androgen that creates libido in both sexes. phragm is that it is nonhormonal. When used properly and regularly, diaphragms are highly eff ective (97–99%). However, Contraceptives Are Designed they are not always used because they must be inserted close to the time of intercourse, and consequently about 20% of women to Prevent Pregnancy who depend on diaphragms for contraception are pregnant One disadvantage of sexual intercourse for pleasure rather than within the fi rst year. Another female barrier contraceptive that reproduction is the possibility of an unplanned pregnancy. On was recently reintroduced is the contraceptive sponge, which average, 85% of young women who have sexual intercourse contains a spermicidal chemical.

926 Reproduction and Development

low failure rates (0.5% per year) but side eff ects that range from Table pain and bleeding to infertility caused by pelvic infl ammatory 26.1 Effi cacy of Various Contraceptive Methods disease and blockage of the fallopian tubes.

Pregnancy Rate With Hormonal Treatments Techniques for decreasing gam- Method Typical Use* ete production depend on altering the hormonal milieu of the body. In centuries past, women would eat or drink various plant No contraception 85% concoctions for contraception. Some of these substances actu- Spermicides 29% ally worked because the plants contained estrogen-like com- pounds. Modern pharmacology has improved on this method, Abstinence during times 25% and now women can choose between oral contraceptive pills, of predicted fertility injections lasting three months, or a vaginal contraceptive ring (NuvaRing ). Diaphragm, cervical cap, 16–32%† ® Th e oral contraceptives, also known as birth control pills, or sponge fi rst became available in 1960. Th ey rely on various combina- Oral contraceptive pills 8% tions of estrogen and progesterone that inhibit gonadotropin secretion from the pituitary. Without adequate FSH and LH, Intrauterine devices (IUDs) < 1% ovulation is suppressed. In addition, progesterones in the con- traceptive pills thicken the cervical mucus and help prevent Contraceptive hormone < 1% injection sperm penetration. These hormonal methods of contracep- tion are highly effective when used correctly but also carry Male condom 15% some risks, including an increased incidence of blood clots and strokes, especially in women who smoke. Female condom 21% Development of a male hormonal contraceptive has been Sterilization < 1% slow because of undesirable side effects. Contraceptives that block testosterone secretion or action are also likely to decrease 26 * Rates reflect unintentional pregnancies in the first year of using the the male libido or even cause impotence. Both side effects method. Data are from www.contraceptivetechnology.org/table.html are unacceptable to men who would be most interested in using (Accessed 7/22/11). the contraceptive. Some early male oral contraceptives irrevers- † Lower rates are in women who have never delivered a child. ibly suppressed sperm production, which was also unacceptable. It now appears, however, that a combination of oral proges- tin to suppress sperm production plus injected testosterone to The male barrier contraceptive is the condom, a closed maintain libido is a promising candidate for a male hormonal sheath that fi ts closely over the penis to catch ejaculated semen. contraceptive. Males have used condoms made from animal bladders and in- Contraceptive vaccines are based on antibodies against testines for centuries. Condoms lost popularity when oral con- various components of the male and female reproductive sys- traceptives came into widespread use in the 1960s and 1970s, tems, such as antisperm or antiovum antibodies. Th ese contra- but in recent years they have regained favor because they com- ceptives can be administered as shots. However, clinical trials of bine pregnancy protection with protection from many sexually human vaccines have been disappointing and vaccines may not transmitted diseases. However, latex condoms may cause aller- be a practical contraceptive for humans. gic reactions, and there is evidence that HIV can pass through pores in some condoms currently produced. A female version of the condom is also commercially available. It covers the cer- Infertility Is the Inability to Conceive vix and completely lines the vagina, providing more protection While some couples are trying to prevent pregnancy, others are from sexually transmitted diseases. spending thousands of dollars trying to get pregnant. Infertility is the inability of a couple to conceive a child aft er a year of un- Implantation Prevention Some contraceptive methods do protected intercourse. For years, infertile couples had no choice not prevent fertilization but do keep a fertilized egg from es- but adoption if they wanted to have a child, but incredible tablishing itself in the endometrium. Th ey include intrauterine strides have been made in this fi eld since the 1970s. As a result, devices (IUDs) as well as chemicals that change the properties many infertile couples today are able to have children. of the endometrium. IUDs are copper-wrapped plastic devices Infertility can arise from a problem in the male, the female, that are inserted into the uterine cavity, where they create a mild or both. Male infertility usually results from a low sperm count inflammatory reaction that prevents implantation. They have or an abnormally high number of defective sperm. Female

927 Reproduction and Development

infertility can be mechanical (blocked fallopian tubes or other Normally, capacitation takes place in the female reproduc- structural problems) or hormonal, leading to decreased or ab- tive tract, which presents a problem for in vitro fertilization. sent ovulation. One problem involving both partners is that the Th ose sperm must be artifi cially capacitated by placing them in woman may produce antibodies to her partner’s sperm. In addi- physiological saline supplemented with human serum. Much tion, not all pregnancies go to a successful conclusion. By some of what we know about human fertilization has come from in- estimates, as many as a third of all pregnancies spontaneously fertility research aimed at improving the success rate of in vitro terminate—many within the fi rst weeks, before the woman is fertilization. even aware that she was pregnant. Fertilization of an egg by a sperm is the result of a chance Some of the most dramatic advances have been made in encounter, possibly aided by chemical attractants produced by the fi eld of assisted reproductive technology (ART), strategies the egg. An egg can be fertilized for only about 12–24 hours af- in which both sperm and eggs are manipulated. For in vitro fer- ter ovulation. Sperm in the female reproductive tract remain vi- tilization, a woman’s ovaries are manipulated with hormones to able for 5–6 days. ovulate multiple eggs at one time. Th e eggs are collected surgi- Fertilization normally takes place in the distal part of the cally and fertilized outside the body. Th e developing embryos fallopian tube. Of the millions of sperm in a single ejaculation, are then placed in the woman’s uterus, which has been primed only about 100 reach this point. To fertilize the egg, a sperm for pregnancy by hormonal therapy. Because of the expense must penetrate both an outer layer of loosely connected granu- and complicated nature of the procedure, multiple embryos are losa cells (the corona radiata) and a protective glycoprotein coat usually placed in the uterus at one time, which may result in called the zona pellucida ( Fig. 26.14 b). To get past these bar- multiple births. In vitro fertilization has allowed some infertile riers, capacitated sperm release powerful enzymes from the ac- couples to have children, with a 2009 success rate in the United rosome in the sperm head, a process known as the acrosomal States averaging 31%. Success varies signifi cantly with age, rang- reaction . Th e enzymes dissolve cell junctions and the zona pel- ing from 41% for women younger than 35 to 12% for women lucida, allowing the sperm to wiggle their way toward the egg. older than 40. Th e fi rst sperm to reach the egg quickly fi nds sperm-bind- ing receptors on the oocyte membrane and fuses its membrane to the egg membrane (Fig. 26.14 c). Th e fused section of mem- Pregnancy and Parturition brane opens, and the sperm nucleus sinks into the egg’s cyto- plasm. Fusion of the egg and sperm membranes signals the egg Now let’s return to a recently ovulated egg and some sperm to resume meiosis and complete its second division. Th e fi nal deposited in the vagina and follow them through fertilization, meiotic division creates a second polar body, which is ejected. pregnancy, and parturition , the birth process. At this point, the 23 chromosomes of the sperm join the 23 chromosomes of the egg, creating a zygote nucleus with a full Fertilization Requires Capacitation set of genetic material. The fusion of sperm and oocyte membrane triggers a Once an egg is released from the ruptured follicle, it is swept chemical reaction called the . Membrane- into the fallopian tube by beating cilia. Meanwhile, sperm de- bound cortical granules in the peripheral cytoplasm of the posited in the vagina must go through their final maturation egg release their contents into the space just outside the egg step, capacitation , which enables the sperm to swim rapidly and membrane. These chemicals rapidly alter the membrane and fertilize an egg. Th e process apparently involves the reorganiza- surrounding zona pellucida so that additional sperm cannot tion of molecules in the outer membrane of the sperm head. penetrate or bind. Th e cortical reaction prevents , in which more than one sperm fertilizes an egg. Once an egg is fertilized and becomes a zygote, it begins RUNNING PROBLEM mitosis as it slowly makes its way along the fallopian tube to the uterus, where it will settle for the remainder of the pe- Analysis of Peggy’s postcoital cervical mucus shows riod {gestare, to carry in the womb}. that sperm are present but not moving. Dr. Coddington explains that it is likely that Peggy’s cervical mucus contains antibodies that destroy Larry’s sperm. The Developing Embryo Implants Q 5 : Speculate on how this kind of infertility problem might in the Endometrium be treated. Th e dividing embryo takes four or fi ve days to move through the fallopian tube into the uterine cavity ( Fig. 26.14 d). Under the influence of progesterone, smooth muscle of the tube re- laxes, and transport proceeds slowly. By the time the developing

928 Fertilization must occur within 24 hours of ovulation.

(a) This photograph shows the tremendous difference (b) Capacitated sperm release enzymes from their in order in the sizes of human sperm and egg. to penetrate the cells and zona pellucida surrounding the egg.

First Egg polar body Egg Second meiotic division suspended Cells of Sperm corona radiata

Capacitated sperm Zona pellucida

(c) The first sperm to fuse with the egg fertilizes it.

Sperm and egg plasma Sperm nucleus moves Oocyte nucleus completes Sperm and egg nuclei fuse membranes fuse. into cytoplasm of egg. meiotic division. to form zygote nucleus.

First polar body Second polar body Egg Egg is expelled.

Sperm nucleus

Sperm nucleus

(d) Timing of ovulation, fertilization, and implantation

3 Days 2–4: Cell 4 Day 4–5: division takes place. reaches uterus. 2 Day 1: Inner cell mass Fertilization

Zygote Fallopian tube

Egg Blastocyst 1 Ovulation Ovary Uterus 5 Days 5–9: Blastocyst implants.

929 Reproduction and Development

embryo reaches the uterus, it consists of a hollow ball of about do not mix, but nutrients, gases, and wastes exchange across 100 cells called a blastocyst . the membranes of the villi. Many of these substances move by Some of the outer layer of blastocyst cells will become the simple diff usion, but some, such as maternal antibodies, must chorion, an extraembryonic membrane that will enclose the em- be transported across the membrane. bryo and form the placenta ( Fig. 26.15 a). Th e inner cell mass Th e placenta continues to grow during pregnancy until, by of the blastocyst will develop into the embryo and into other delivery, it is about 20 cm in diameter (the size of a small dinner extraembryonic membranes. These membranes include the plate). Th e placenta receives as much as 10% of the total mater- amnion, which secretes amniotic fl uid in which the developing nal cardiac output. Th e tremendous blood fl ow to the placenta embryo fl oats; the allantois, which becomes part of the umbili- is one reason sudden, abnormal separation of the placenta from cal cord that links the embryo to the mother; and the yolk sac, the uterine wall is a medical emergency. which degenerates early in human development. Implantation of the blastocyst into the uterine wall nor- mally takes place about 7 days aft er fertilization. Th e blasto- The Placenta Secretes Hormones cyst secretes enzymes that allow it to invade the endometrium, like a parasite burrowing into its host. As it does so, endome- During Pregnancy trial cells grow out around the blastocyst until it is completely As the blastocyst implants in the uterine wall and the placenta engulfed. begins to form, the corpus luteum is nearing the end of its pre- As the blastocyst continues dividing and becomes an em- programmed 12-day life span. Unless the developing embryo bryo, cells that will become the placenta form fi ngerlike cho- sends a hormonal signal, the corpus luteum disintegrates, pro- rionic villi that penetrate into the vascularized endometrium. gesterone and estrogen levels drop, and the embryo is fl ushed Enzymes from the villi break down the walls of maternal blood from the body along with the surface layers of endometrium vessels until the villi are surrounded by pools of maternal blood during menstruation. Several hormones that prevent menstrua- ( Fig. 26.15 b). Th e blood of the embryo and that of the mother tion during pregnancy are secreted by the placenta, including

THE PLACENTA

(a) The developing embryo floats in . It (b) Some material is exchanged across placental obtains oxygen and nutrients from the mother membranes by diffusion, but other material through the placenta and umbilical cord. must be transported.

Umbilical vein carries Umbilical arteries well-oxygenated return embryonic blood to the embryo. blood to placenta. Umbilical cord

Placenta

Chorionic villi contain embryonic blood vessels.

Extraembryonic membranes enclose the embryo and form the placenta. Umbilical cord Maternal blood Yolk sac bathes the chorionic villi. Amniotic Chorion fluid Amnion

WEEK 10 Maternal blood vessels

Amnion Fig. 26.15

930 Reproduction and Development human chorionic gonadotropin, human placental lactogen, es- Human Placental Lactogen (hPL) Another peptide hormone trogen, and progesterone. produced by the placenta is human placental lactogen (hPL), also known as human chorionic somatomammotropin (hCS). Human Chorionic Gonadotropin Th e corpus luteum remains Th is hormone, structurally related to growth hormone and pro- active during early pregnancy because of human chorionic lactin, was initially believed to be necessary for breast develop- gonadotropin (hCG), a peptide hormone secreted by the cho- ment during pregnancy and for milk production (lactation). rionic villi and developing placenta. Human chorionic gonado- Although hPL probably does contribute to lactation, women tropin is structurally related to LH, and it binds to LH receptors. who do not make hPL during pregnancy because of a genetic de- Under the infl uence of hCG, the corpus luteum keeps produc- fect still have adequate breast development and milk production. ing progesterone to keep the endometrium intact. A second role for hPL is alteration of the mother’s glucose By the seventh week of development, however, the placenta and fatty acid metabolism to support fetal growth. Maternal glu- has taken over progesterone production, and the corpus luteum cose moves across the membranes of the placenta by facilitated is no longer needed. At that point, it fi nally degenerates. Human diffusion and enters the fetal circulation. During pregnancy, chorionic gonadotropin production by the placenta peaks at about 4% of women develop gestational diabetes mellitus, with el- three months of development, then diminishes. evated blood glucose levels caused by insulin resistance, similar A second function of hCG is stimulation of testosterone to type 2 diabetes. Aft er delivery, glucose metabolism in most of production by the developing testes in male fetuses. As you these women returns to normal, but these mothers and their ba- learned in the opening sections of this chapter, fetal testoster- bies are at higher risk of developing type 2 diabetes later in life. one and its metabolite DHT are essential for expression of male characteristics and for descent of the testes into the scrotum be- Estrogen and Progesterone Estrogen and progesterone are fore birth. produced continuously during pregnancy, first by the corpus Human chorionic gonadotropin is the chemical detected luteum under the infl uence of hCG and then by the placenta. by pregnancy tests. Because hCG can induce ovulation in rab- With high circulating levels of these steroid hormones, feedback bits, years ago rabbits were used for pregnancy testing. If a suppression of the pituitary continues throughout pregnancy, woman suspected she was pregnant, her urine was injected into preventing another set of follicles from beginning development. a rabbit. The rabbit’s ovaries were then inspected for signs of During pregnancy, estrogen contributes to the develop- 26 ovulation. It took several days for women to learn the results of ment of the milk-secreting ducts of the . Progesterone this test. Today, with modern biochemical techniques, women is essential for maintaining the endometrium and in addition can perform their own pregnancy tests in a few minutes in the helps suppress uterine contractions. Th e placenta makes a vari- privacy of their home. ety of other hormones, including inhibin and prorenin, but the function of most of them remains unclear.

RUNNING PROBLEM Pregnancy Ends with Labor and Delivery Parturition normally occurs between the 38th and 40th week Assisted reproductive technologies (ART) are one treatment option currently available to infertile couples. All ART of gestation. What triggers this process? For many years, re- techniques involve either artifi cially stimulating the ovaries to searchers developed animal models of the signals that initiate produce eggs or using an egg from an egg donor. The eggs parturition, only to discover recently that there are no good are harvested surgically and are fertilized in vitro . The zygote non-primate models that apply to humans. Parturition begins may be placed in the fallopian tube immediately or may be with labor, the rhythmic contractions of the uterus that push allowed to develop into an early embryo before being placed the fetus out into the world. Signals that initiate these contrac- into the uterus. A diff erent technique used to overcome tions could begin with either the mother or the fetus, or they infertility is intrauterine . In this procedure, sperm could be a combination of signals from both. that have been washed to remove antigenic material are In many nonhuman mammals, a decrease in estrogen and introduced into the uterus through a tube inserted through progesterone levels marks the beginning of parturition. A de- the cervix so that fertilization takes place in vivo . crease in progesterone levels is logical, as progesterone inhibits Q6: Based on the results of their infertility workup, which uterine contractions. In humans, however, levels of these hor- intervention—ART or intrauterine insemination—should mones do not decrease until labor is well under way. be recommended for Peggy and Larry? Why? Another possible labor trigger is oxytocin, the peptide hormone that causes uterine muscle contraction. As a preg- nancy nears full term, the number of uterine oxytocin receptors increases. However, studies have shown that oxytocin secretion does not increase until aft er labor begins. Synthetic oxytocin is

931 Reproduction and Development

oft en used to induce labor in pregnant women, but it is not al- off spring at a time, have two functional mammary glands. A ways eff ective. Apparently, the start of labor requires something mammary gland is composed of 15–20 milk-secreting lobes more than adequate amounts of oxytocin. ( Fig. 26.17 a ). Each lobe branches into lobules, and the lob- Another possibility is that the fetus somehow signals that ules terminate in secretory structures called alveoli or acini. it has completed development. One theory supported by clini- Each alveolus is composed of secretory epithelium that secretes cal evidence is that corticotropin-releasing hormone (CRH) se- into a duct, similar to the exocrine secretions of the pancreas. creted by the placenta is the signal to begin labor. (CRH is also Each alveolus is surrounded by contractile myoepithelium . In- a hypothalamic releasing factor that controls release of ACTH terestingly, the mammary gland epithelium is closely related to from the anterior pituitary.) In the weeks prior to delivery, ma- the secretory epithelium of sweat glands, so milk secretion and ternal blood CRH levels increase rapidly. In addition, women sweat secretion share some common features. with elevated CRH levels as early as 15 weeks of gestation are During puberty, the breasts begin to develop under the more likely to go into premature labor. infl uence of estrogen. Th e milk ducts grow and branch, and Although we do not know for certain what initiates parturi- fat is deposited behind the glandular tissue. During preg- tion, we do understand the sequence of events. In the days prior nancy, the glands develop further under the direction of es- to the onset of active labor, the cervix softens (“ripens”) and trogen, growth hormone, and cortisol. Th e fi nal development ligaments holding the pelvic bones together loosen as enzymes step also requires progesterone, which converts the duct epi- destabilize collagen in the connective tissue. Th e control of these thelium into a secretory structure. Th is process is similar to processes is not clear and may be due to estrogen or the peptide progesterone’s effect on the uterus, in which progesterone hormone relaxin, which is secreted by ovaries and the placenta. makes the endometrium into a secretory tissue during the lu- Once the contractions of labor begin, a positive feed- teal phase. back loop consisting of mechanical and hormonal factors is Although estrogen and progesterone stimulate mammary set into motion. The fetus is normally oriented head down development, they inhibit secretion of milk. Milk production ( Fig. 26.16 a). At the beginning of labor it repositions itself is stimulated by prolactin from the anterior pituitary. Prolactin lower in the abdomen (“the baby has dropped”) and begins to is an unusual pituitary hormone in that its secretion is primar- push on the soft ened cervix (Fig. 26.16 b). ily controlled by prolactin-inhibiting hormone (PIH) from Cervical stretch triggers uterine contractions that move the hypothalamus. Good evidence suggests that PIH is actually in a wave from the top of the uterus down, pushing the fetus dopamine, an amine neurohormone related to epinephrine and farther into the pelvis. The lower portion of the uterus stays norepinephrine. relaxed, and the cervix stretches and dilates. Cervical stretch During the later stages of pregnancy, PIH secretion falls, starts a positive feedback cycle of escalating contractions (Fig. and prolactin reaches levels 10 or more times those found in 26.16 d). Th e contractions are reinforced by secretion of oxyto- nonpregnant women. Prior to delivery, when estrogen and cin from the posterior pituitary, with continued cervical stretch progesterone are also high, the mammary glands produce only reinforcing oxytocin secretion. small amounts of a thin, low-fat secretion called colostrum . Prostaglandins are produced in the uterus in response to After delivery, when estrogen and progesterone decrease, the oxytocin and CRH secretion. Prostaglandins are very eff ective glands produce greater amounts of milk that contains 4% fat at causing uterine muscle contractions at any time. They are and substantial amounts of calcium. Proteins in colostrum and the primary cause of menstrual cramps and have been used to milk include maternal immunoglobulins, secreted into the duct induce abortion in early pregnancy. During labor and delivery, and absorbed by the infant’s intestinal epithelium. Th is process prostaglandins reinforce the uterine contractions induced by transfers some of the mother’s immunity to the infant during its oxytocin ( Fig. 26.16 d). fi rst weeks of life. As the contractions of labor intensify, the fetus moves down Suckling , the mechanical stimulus of the infant nursing though the vagina and out into the world ( Fig. 26.16 c), still at- at the breast, reinforces the inhibition of PIH begun in the last tached to the placenta. Th e placenta then detaches from the uterine weeks of pregnancy ( Fig. 26.17 b). In the absence of PIH, prolac- wall and is expelled a short time later. Uterine contractions clamp tin secretion increases, resulting in milk production. Pregnancy the maternal blood vessels and help prevent excessive bleeding, al- is not a requirement for lactation, and some women who have though typically the mother loses about 240 mL of blood. adopted babies have been successful in breast-feeding. The ejection of milk from the glands, known as the let- The Mammary Glands Secrete Milk down refl ex, requires the presence of oxytocin from the poste- rior pituitary. Oxytocin initiates smooth muscle contraction in During Lactation the uterus and breasts. In the postpartum (aft er delivery) uterus, A newborn has lost its source of maternal nourishment oxytocin-induced contractions help return the uterus to its pre- through the placenta and must rely on an external source of pregnancy size. food instead. Primates, who normally have only one or two

932 Reproduction and Development

PARTURITION: THE BIRTH PROCESS

(a) Fully developed fetus. As labor begins, the (d) The process of labor is controlled by a positive fetus is normally head down in the uterus. feedback loop that ends with delivery.

Umbilical Fetus cord drops lower in uterus.

+ Cervix Placenta Cervical Vagina stretch Cervical canal +

Oxytocin from + Uterine posterior pituitary contractions + +

Prostaglandins from uterine wall

(b) . Uterine contractions push the head against the softened cervix, stretching and dilating it.

Delivery of baby 26 stops the cycle.

(c) Delivery. Once the cervix is fully dilated and stretched, the uterine contractions push the fetus out through the vagina.

Fig. 26.16

933 Reproduction and Development

LACTATION

(a) Mammary glands (b) The hormonal control of milk secretion and release

Epithelial cells of the mammary glands secrete milk into the Prolactin controls milk secretion, and oxytocin causes ducts of the gland. Contraction of the myoepithelium forces smooth muscle contraction to eject milk. fluid out of the ducts through openings in the nipple.

Higher Sound of brain Pectoralis major child's cry centers muscle Pectoral fat pad

Suspensory Hypothalamus - ligaments + PIH cell Lobes of glandular tissue Oxytocin neuron

Milk duct

Nipple Portal system Areola

PIH Posterior Anterior pituitary pituitary Ascending sensory information

Inhibition of prolactin cells is removed.

Prolactin Oxytocin

Mammary gland lobule

Milk secretion

Milk Smooth muscle ejected contraction Milk duct

Muscle cells in wall of duct

Epithelial Baby Mechanoreceptors milk-secreting cells suckling in nipple Myoepithelial cells

Mammary gland alveolus Fig. 26.17

In the lactating breast, oxytocin causes contraction of myo- release requires the mechanical stimulus of suckling, oxytocin re- epithelial cells surrounding the alveoli and in the walls of the lease can be stimulated by various cerebral stimuli, including the ducts. Contraction creates high pressure in the ducts that sends thought of the child. Many nursing mothers experience inappro- the milk squirting into the infant’s mouth. Although prolactin priate milk release triggered by hearing someone else’s child cry.

934 Reproduction and Development

Prolactin Has Other Physiological Roles If a woman did not start her menstrual periods until she was 16, for example, it is likely that her daughters will also have late Although we discussed prolactin in the context of nursing . mothers, all non-nursing women and men have tonic prolac- Th e adipose tissue hormone leptin also contributes to the tin secretion that exhibits a diurnal cycle, peaking during sleep. onset of puberty. Undernourished women with little adipose tis- Prolactin is related to growth hormone and plays a role in other sue and low leptin levels oft en stop having menstrual periods reproductive and nonreproductive processes. For example, pro- (amenorrhea ), and knockout mice without leptin are infertile. lactin is synthesized in the uterine endometrium during normal Presumably improved nutrition over the last century increased menstrual cycles. Male knockout mice who lack prolactin or a individuals’ prepubertal fat stores and leptin secretion, which prolactin receptor have decreased fertility. could interact with other factors to initiate puberty. Some interesting research has established a role for pro- lactin in neuroimmunomodulation. Both prolactin and growth hormone appear to be necessary for normal diff erentiation of T Menopause and Andropause lymphocytes in the thymus gland, an observation supported by Are a Consequence of Aging impaired immune function in animals with hypoprolactinemia . In nineteenth century America, many people died of acute ill- In contrast, several autoimmune diseases, including multiple nesses while still reproductively active. Now modern medicine sclerosis, systemic lupus erythematosus, and autoimmune thy- has overcome most acute illnesses, and most of us will live well roiditis, have been linked to elevated levels of prolactin. past the time we are likely to have children. Women’s reproductive cycles stop completely at the time known as menopause . Th e physiology of menopause has been Growth and Aging well studied. Aft er about 40 years of menstrual cycles, a woman’s periods become irregular (perimenopause ) and fi nally cease. Th e Th e reproductive years begin with the events surrounding pu- cessation of reproductive cycles is due not to the pituitary but to berty and end with decreasing gonadal hormone production. the ovaries, which can no longer respond to gonadotropins. In the absence of negative feedback, gonadotropin levels increase Puberty Marks the Beginning dramatically in an eff ort to stimulate the ovaries into maturing 26 more follicles. of the Reproductive Years Th e absence of estrogen in postmenopausal women leads In girls, the onset of puberty is marked by budding breasts and to symptoms of varying severity. Th ese may include hot fl ashes, the fi rst menstrual period, called menarche, a time of ritual sig- atrophy of genitalia and breasts, and osteoporosis as calcium nifi cance in many cultures. In the United States, the average age at is lost from bones. Hormone replacement therapy (HRT) for menarche is 12 years (normal range is considered 8 to 13 years). women in menopause traditionally consists of estrogen or a In boys, the onset of puberty is more subtle. Th e signs in- combination of estrogen and progesterone. Th is treatment has clude growth and maturation of the external genitalia; develop- become controversial, however, because of some studies that ment of secondary sex characteristics, such as pubic and facial suggest that HRT risks outweigh its benefi ts. hair and lowering of voice pitch; change in body shape; and A newer drug therapy for menopause uses selective estro- growth in height. Th e age range for male puberty is 9 to 14 years. gen receptor modulators (SERMs). Th ese drugs bind with diff er- Puberty requires maturation of the hypothalamic-pituitary ent affi nities to the two estrogen receptor subtypes, which allows control pathway. Before puberty, the child has low levels of both the drugs to mimic the beneficial effects of estrogen on bone steroid sex hormones and gonadotropins. Because low sex hor- while avoiding the potentially detrimental eff ects on breasts and mone levels normally enhance gonadotropin release, the combi- uterus. nation of low steroids and low gonadotropins indicates that the In men, testosterone production decreases with age, and hypothalamus and pituitary are not yet sensitive to steroid levels about half of men over the age of 50 have symptoms of andro- in the blood. pause, a term coined as the counterpart to menopause. Th e ex- At puberty, the hypothalamic GnRH-secreting neurons in- istence of physiological andropause in men is still controversial crease their pulsatile secretion of GnRH, which in turn increases because the physical and psychological symptoms of aging in gonadotropin release. Th e signals responsible for the onset of men are not clearly linked to a decline in testosterone. Many puberty are complex, but several of them appear to be mediated men remain reproductively active as they age, and it is not un- by the hypothalamic neuropeptide kisspeptin. One theory holds common for men in their fi ft ies or sixties to have children with that the genetically programmed maturation of hypothalamic younger women. Postmenopausal women also remain sexually neurons initiates puberty. We know that puberty has a genetic active, although not reproductively active, and some report a basis because inherited patterns of maturation are common. more fulfi lling sex life once the fear of unwanted pregnancy has been removed.

935 Reproduction and Development

RUNNING PROBLEM CONCLUSION

Infertility Peggy and Larry used home ovulation tests that measured more about infertility, see literature from the American Peggy’s LH levels to determine when she was ovulating. Society for at www.asrm.org or On the day her LH surged, Peggy went to her doctor’s go to Medline Plus ( www.nlm.nih.gov/medlineplus) and offi ce, where a washed sperm sample was inserted into look under Health Topics. The Centers for Disease Control her uterus through a small tube. After the third cycle keep statistics on the success of assisted reproductive Peggy became pregnant and later gave birth to a little technologies (ART) on their web site (www.cdc.gov ). girl. Now test your understanding of the running problem In this running problem you learned how the cause by checking your answers against the information in this of infertility is diagnosed in a typical couple. To learn summary table.

Question Facts Integration and Analysis

1. Name (in order) the male The male reproductive structures include the Sperm leaving the testes pass into the epididy- reproductive structures that testes, accessory glandular organs, a series of mis, then into the vas deferens, and fi nally exit carry sperm from the testes ducts, and the external genitalia. the body via the urethra. to the external environment.

2. Which causes of male in- The epididymis is the fi rst duct the sperm If the infertility problem is due to blockage or fertility might make retrieval enter upon leaving the testes. congenital defects in the vas deferens or urethra, of sperm from the epididymis removal of sperm from the epididymis might be necessary? useful. If the problem is caused by low sperm count or abnormal sperm morphology, this technique would probably not be useful.

3. For which causes of female Basal body temperature rises slightly follow- Temperature tracking is a useful way to tell if a infertility is temperature ing ovulation. woman is ovulating, but it cannot reveal struc- tracking useful? For which tural problems in the female reproductive tract. causes is it not useful?

4. What abnormalities in the The cervix, fallopian tubes, and uterus are Any blockage of these organs resulting from dis- cervix, fallopian tubes, and hollow structures through which sperm must ease or congenital defects would prevent normal uterus could cause infertility? pass. movement of sperm and cause infertility. Hor- monal problems might cause the endometrium to develop incompletely, preventing implanta- tion of the embryo.

5. Speculate on how infertil- Antibodies in the cervical mucus react If the antigenic material can be removed from ity due to cervical mucus an- with antigenic material in the semen or on the semen, this might help the problem of sperm tibodies against sperm might the sperm, causing the sperm to become immobilization. A semen sample can be washed be treated. immobile. to remove nonsperm components. If the antigens are part of the sperm, this method will not work.

6. Should ART or intrauterine ART is used when ovulation is abnormal. Intrauterine insemination can be used to over- insemination be recom- Intrauterine insemination is used when ovula- come cervical factors, as this technique bypasses mended for Peggy and Larry? tion is normal. the cervix. Because Peggy can ovulate, she and Why? Larry should try intrauterine insemination fi rst.

Test your understanding with: • Practice Tests • PhysioExTM Lab Simulations • Running Problem Quizzes • Interactive Physiology TM • A&PFlix Animations Animations www.masteringaandp.com

936 Reproduction and Development

Chapter Summary

In this chapter you learned how the human species perpetuates itself cycle, when the feedback eff ects of estrogen change from negative to posi- through reproduction. The reproductive system has some of the most tive and back again. An example of positive feedback occurs with oxytocin complex control systems of the body, in which multiple hormones interact secretion during labor and delivery. Th e testis provides a nice example in an ever-changing fashion. Homeostasis in the adult reproductive sys- of compartmentation , with the lumen of the seminiferous tubules, where tem is anything but steady state, particularly during the female menstrual sperm develop, isolated from the rest of the extracellular compartment.

Sex Determination Male Reproduction 1. Th e sex organs consist of gonads, internal genitalia , and external 14. Th e corpus spongiosum and corpora cavernosa make up the erec- genitalia. tile tissue of the penis. Th e glans is covered by the foreskin. Th e ure- 2. Testes produce sperm . Ovaries produce eggs, or ova. Embryonic thra runs though the penis. ( Fig. 26.7 ) cells that will produce gametes (eggs and sperm) are called germ 15. Th e testes migrate into the scrotum during fetal development. Fail- cells. ure of one or both testes to descend is known as cryptorchidism . 3. Humans have 46 chromosomes. ( Fig. 26.1 a) 16. Th e testes consist of seminiferous tubules and interstitial tissue con- 4. Th e genetic sex of an individual depends on the sex chromosomes: taining blood vessels and Leydig cells. Th e seminiferous tubules join females are XX, and males are XY. In the absence of a Y chromo- the epididymis, which becomes the vas deferens. Th e vas deferens some, an embryo will develop into a female. (Fig. 26.1 b) empties into the urethra. ( Fig. 26.7 b) 5. Th e SRY gene on the Y chromosomes produces SRY protein, a tes- 17. A seminiferous tubule contains spermatogonia, spermatocytes, and tis-determining factor that converts the bipotential gonad into a tes- Sertoli cells. Tight junctions between Sertoli cells form a blood- tis. In the absence of SRY protein, the gonad becomes an ovary. testis barrier. ( Fig. 26.7 d, e) 6. Testicular Sertoli cells secrete anti-Müllerian hormone (AMH), 18. Spermatogonia in the tubule undergo meiosis, becoming primary which causes the Müllerian ducts to regress. Leydig cells secrete tes- spermatocytes, spermatids, and fi nally sperm in about 64 days. (Fig. tosterone, which converts Wolffi an ducts to male accessory struc- 26.7 e) tures. Dihydrotestosterone (DHT) promotes development of the 19. Sertoli cells regulate sperm development. They also produce in- prostate gland and external genitalia. (Fig. 26.2 ) hibin, activin, growth factors, enzymes, and androgen-binding pro- 7. Absence of testosterone and AMH causes Müllerian ducts to de- tein . ( Fig. 26.8 ) 26 velop into fallopian tubes (oviducts), uterus, and vagina. In fe- 20. Leydig cells produce 95% of a male’s testosterone. The other 5% males, the Wolffi an ducts regress. ( Fig. 26.2 ) comes from the adrenal cortex. 21. FSH stimulates Sertoli cell production of androgen-binding protein, Basic Patterns of Reproduction inhibin, and paracrine molecules. Leydig cells produce testosterone under the direction of LH. (Fig. 26.8 ) 8. Gametogenesis begins with mitotic divisions of spermatogonia and oögonia . Th e fi rst step of meiosis creates primary spermatocytes 22. Th e prostate gland , seminal vesicles, and bulbourethral glands se- and primary oocytes . Th e fi rst meiotic division creates two identical crete the fl uid component of semen . secondary spermatocytes in males or a large secondary oocyte (egg) 23. Primary sex characteristics are the internal sexual organs and exter- and a tiny fi rst polar body in females. ( Fig. 26.5 ) nal genitalia. Secondary sex characteristics are other features of the 9. The second meiotic division in males creates haploid spermatids body, such as body shape. that mature into sperm. In females, the second meiotic division does not take place unless the egg is fertilized. (Fig. 26.5 ) Female Reproduction 10. In both sexes, gonadotropin-releasing hormone (GnRH) controls the secretion of follicle-stimulating hormone (FSH) and luteinizing 24. Female external genitalia, called the vulva or pudendum, are the hormone (LH) from the anterior pituitary. FSH and steroid sex hor- labia majora, labia minora, and clitoris. Th e urethra opening is be- mones regulate gametogenesis in gonadal gamete-producing cells. tween the clitoris and the vagina. (Fig. 26.9 ) LH stimulates production of steroid sex hormones. ( Fig. 26.6 ) 25. Th e uterine tissue layers are outer connective tissue, myometrium, 11. Th e steroid sex hormones include androgens , estrogens , and pro- and endometrium. ( Fig. 26.9 d) gesterone. Aromatase converts androgens to estrogens. Inhibin in- 26. Fallopian tubes are lined with ciliated epithelium. Th e bulk of an hibits secretion of FSH, and activin stimulates FSH secretion. ovary consists of ovarian follicles. (Fig. 26.9 e) 12. Gonadal steroids generally suppress secretion of GnRH, FSH, and 27. Eggs are produced in monthly menstrual cycles. ( Fig. 26.10 ) LH. However, if estrogen rises rapidly above a threshold level for at 28. In the ovarian cycle, the follicular phase is a period of follicular least 36 hours, its feedback changes to positive and stimulates go- growth. Ovulation is the release of an egg from its follicle. In the nadotropin release. luteal phase, the ruptured follicle becomes a corpus luteum. ( Fig. 13. A ft er puberty, tonic GnRH release occurs in small pulses every 1–3 26.10 ) hours from a region of the hypothalamus called a pulse generator . 29. Th e menses begin the uterine cycle. Th is is followed by a prolifera- tive phase, with endometrial thickening. Following ovulation, the endometrium goes into a secretory phase. ( Fig. 26.10 )

937 Reproduction and Development

30. Follicular granulosa cells secrete estrogen. As the follicular phase 41. Th e developing embryo is a hollow blastocyst when it reaches the ends, a surge in LH is necessary for oocyte maturation. (Fig. 26.10 ) uterus. Once the blastocyst implants, it develops extraembryonic 31. Th e corpus luteum secretes progesterone and some estrogen, which membranes. ( Figs. 26.14 d and 26.15 ) exert negative feedback on the hypothalamus-anterior pituitary. 42. Th e chorionic villi of the placenta are surrounded by pools of ma- ( Fig. 26.12 ) ternal blood where nutrients, gases, and wastes are exchanged be- 32. Estrogens and androgen control primary and secondary sex charac- tween mother and embryo. ( Fig. 26.15 ) teristics in females. 43. Th e corpus luteum remains active during early pregnancy because of human chorionic gonadotropin (hCG) produced by the develop- Procreation ing embryo. 44. The placenta secretes hCG, estrogen, progesterone, and human 33. Th e human sex act is divided into four phases; (1) excitement, (2) placental lactogen . This last hormone plays a role in maternal plateau, (3) orgasm, and (4) resolution. metabolism. 34. Th e male erection refl ex is a spinal refl ex that can be infl uenced by 45. Estrogen during pregnancy contributes to development of milk- higher brain centers. Parasympathetic input mediated by nitric ox- secreting ducts in the breasts. Progesterone is essential for main- ide actively vasodilates the penile arterioles. (Fig. 26.13 ) taining the endometrium and, along with relaxin, helps suppress 35. Emission is the movement of sperm out of the vas deferens and into uterine contractions. the urethra. Ejaculation is the expulsion of semen to the external 46. Parturition normally occurs between the 38th and 40 th week of ges- environment. tation. It begins with labor and ends with delivery of the fetus and 36. Contraceptive methods include abstinence, barrier methods, im- placenta. A positive feedback loop of oxytocin secretion causes uter- plantation prevention, and hormonal treatments. ine muscle contraction. ( Fig. 26.16 ) 37. Infertility can arise from a problem in the male, the female, or both. 47. Following delivery, the mammary glands produce milk under the In vitro fertilization has allowed some infertile couples to have infl uence of prolactin. Milk is released during nursing by oxytocin, children. causing mammary gland myoepithelial cells to contract. (Fig. 26.17 ) 48. Prolactin plays a role in immune function in both sexes. Pregnancy and Parturition 38. Sperm must go through capacitation before they can fertilize an Growth and Aging egg. 49. In girls, puberty begins with menarche, the fi rst menstrual period, 39. Fertilization normally takes place in the fallopian tube. Capaci- at age 8–13 years. Th e age range for the onset of puberty in boys is 9 tated sperm release acrosomal enzymes (the acrosomal reaction) to to 14 years. dissolve cell junctions and the zona pellucida of the egg. Th e fi rst 50. The cessation of reproductive cycles in women is known as the sperm to reach the egg fertilizes it. (Fig. 26.14 ) menopause. With increasing age, some men exhibit symptoms of 40. Fusion of egg and sperm membranes initiates a cortical reaction testosterone defi ciency. that prevents polyspermy.

Questions

The Physiology Place 5. D e fi ne each of the following terms and describe its signifi cance to reproductive physiology: Level One Reviewing Facts and Terms (a) aromatase 1. Match each of the following items with all the terms it applies to: (b) blood-testis barrier (c) androgen-binding protein 1. chromosomes other than (a) X or Y (d) fi rst polar body sex chromosomes (b) inactivated X chromosome (e) acrosome (c) XX 2. fertilized egg 6. Decide whether each of the following statements is true or false, and (d) XY 3. sperm or ova defend your answer. (e) XX or XY 4. sex chromosomes (f) autosomes 5. germ cells (a) All testosterone is produced in the testes. 6. male chromosomes (b) Each sex hormone is produced only by members of one sex. 7. female chromosomes (c) Anabolic steroid use appears to be addictive, and withdrawal 8. Barr body symptoms include psychological disturbances. (d) High levels of estrogen in the late follicular phase help prepare 2. Th e Y chromosome contains a region for male sex determination the uterus for menstruation. that is known as the gene. (e) Progesterone is the dominant hormone of the luteal phase of 3. List the functions of the gonads. How do the products of gonadal the ovarian cycle. function diff er in males and females? 7. What is semen? What are its main components, and where are they 4. Trace the anatomical routes to the external environment followed produced? by a newly formed sperm and by an ovulated egg. Name all struc- 8. List and give a specifi c example of the various methods of contra- tures the gametes pass through on their journey. ception. Which is/are most eff ective? Least eff ective?

938 Reproduction and Development

Level Two Reviewing Concepts trisomy, using what you have learned about the events surrounding fertilization. 9. Concept maps: Map the following groups of terms. You may add terms. 18. Sometimes the follicle fails to rupture at ovulation, even though it appears to have gone through all stages of development. Th is condi- List 1 List 2 tion results in benign ovarian cysts, and the unruptured follicles can • AMH • antrum be palpated as bumps on the surface of the ovary. If the cysts persist, • DHT • corpus luteum symptoms of this condition often mimic pregnancy, with missed • Leydig cells • endometrium menstrual periods and tender breasts. Explain how these symptoms • Müllerian ducts • follicle occur, using diagrams as needed. • Sertoli cells • granulosa cells 19. An XY individual inherits a mutation that results in completely • sperm • myometrium nonfunctional androgen receptors. • spermatids • ovum • spermatocytes • thecal cells (a) Is this person genetically male or female? • spermatogonia (b) Will this person have functional ovaries, functional testes, or in- • SRY completely developed or nonfunctional gonads? • testosterone (c) Will this person have Wolffi an ducts or their derivatives? Mülle- • Wolffi an ducts rian ducts or their derivatives? (d) Will this person have the external appearance of a male or a 10. Diagram the hormonal control of gametogenesis in males. female? 11. Diagram the menstrual cycle, distinguishing between the ovarian 20. The babies of mothers with gestational diabetes mellitus tend to cycle and the uterine cycle. Include all relevant hormones. weigh more at birth. Th ey are also at risk of developing hypoglyce- 12. Why are X-linked traits exhibited more frequently by males than mia immediately following birth. Use what you have learned about females? diabetes and insulin to explain these two observations. Hint: these 13. D e fi ne and relate each of the following terms in each group: babies have normal insulin responses. (a) gamete, zygote, germ cell, embryo, fetus (b) coitus, erection, ejaculation, orgasm, emission, erogenous zones Level Four Quantitative Problems (c) capacitation, zona pellucida, acrosomal reaction, cortical reac- tion, cortical granules 21. Th e following graph shows the results of an experiment in which nor- (d) puberty, menarche, menopause, andropause mal men were given testosterone over a period of months (indicated by the beige bar from A to E). Control values of hormones were mea- 14. Compare the actions of each of the following hormones in males sured prior to the start of the experiment. From time B to time C, the and females: 26 men were also given FSH. From time D to time E, they were also given (a) FSH LH. Based on the information given, answer the following questions. (b) inhibin (c) activin (d) GnRH 400 FSH LH (e) LH (f) DHT (g) estrogen (h) testosterone mg/mL 200 (i) progesterone LH

15. Compare and contrast the events of the four phases of sexual inter- Plasma gonadotropins FSH course in males and in females. 0 16. Discuss the roles of each of the following hormones in pregnancy, labor and delivery, and mammary gland development and lactation: (a) human chorionic gonadotropin 1000 (b) luteinizing hormone (c) human placental lactogen mg/mL 500 Testosterone (d) estrogen 0 (e) progesterone Plasma testosterone (f) relaxin ABCDE (g) prolactin Months

Level Three Problem Solving (a) Why did testosterone level increase beginning at point A? 17. Down syndrome is a chromosomal defect known as “trisomy” (b) Why did LH and FSH levels decrease beginning at point A? (three copies instead of two) of chromosome 21. The extra chro- (c) Predict what happened to the men’s sperm production in the mosome usually comes from the mother. Speculate what causes A–B interval, the B–C interval, and the D–E interval.

939 Reproduction and Development

Answers

12. Sertoli cells secrete inhibin, activin, androgen-binding protein, en- Answers to Concept Check Questions zymes, and growth factors. Leydig cells secrete testosterone. 13. Th e advantage is that GnRH agonists decrease FSH and LH, so the 1. Female gonad: ovary; female gamete: egg, or ovum. Male gonad: testes stop producing sperm. The disadvantage is that the testes testis; male gametes: sperm. also stop producing testosterone, which causes decreased sex drive. 2. Primary androgen receptors are in the cytoplasm or nucleus of the 14. Cholesterol and steroid hormones such as cortisol are examples of target cell. AMH has membrane receptors. lipophilic molecules that bind to protein carriers. 3 . Th e male parent donates the chromosome that determines sex of 15. Exogenous anabolic steroids (androgens) shut down FSH and LH the zygote; therefore, the wives were not at fault. secretion. In response, the testes shrink and stop producing sperm. 4. An XO fetus will be a female because she lacks a Y chromosome. 16. Ovarian cycle: follicular phase, ovulation, and luteal phase. The 5. Lack of AMH from the testes allows Müllerian ducts to develop menses and proliferative phases of the uterine cycle correspond to into uterus and fallopian tubes. External genitalia will be female the follicular phase and ovulation; the secretory uterine phase cor- because there is no DHT for development of male genitalia. responds to the luteal phase. 6. A newborn male’s gametes are spermatogonia; a newborn female’s 17. Women who take anabolic steroids may experience growth of fa- gametes are primary oocytes. cial and body hair, deepening of the voice, increased libido, and 7 . Th e fi rst polar body has twice as much DNA as the second polar irregular menstrual cycles. body. 18. A woman given an aromatase inhibitor would have decreased es- 8. Each primary oocyte forms one egg; each primary spermatocyte trogen production. forms four sperm. 19. Ovulation occurs about 14 days before the end of the cycle, which 9. Aromatase converts testosterone to estradiol. would be (a) day 14, (b) day 9, or (c) day 17. 10. FSH = follicle-stimulating hormone, DHT = dihydrotestosterone, SRY = sex-determining region of Y chromosome, LH = luteiniz- ing hormone, GnRH = gonadotropin-releasing hormone, AMH = Answers to FiFiguregure Questions anti-Müllerian hormone. 11. Hypothalamic GnRH, and FSH and LH from the anterior pitu- Figure 26.7 : Mitochondria produce ATP to power the fl agellum. itary, control reproduction.

Answers to Review Questions

Level One Reviewing Facts and Terms Level Two Reviewing Concepts 1. (a) 3, 4, 5; (b) 8; (c) 2, 7; (d) 2, 6; (e) 2; (f) 1 9. List 1: use Figures 26.2 , 26.3 , and 26.4 . List 2: use Figures 26.9 , 26.10 , and 26.12 . 2. SRY 10. See Figure 26.8 . 3. Gonads produce gametes and secrete sex hormones. Female gamete—egg (ovum); male—sperm. Female gonadal hormones—estrogen, progesterone, 11. See Figures 26.10 and 26.12 . androgens, and inhibin; male—androgens and inhibin. 12. Males have one Y chromosome, which often does not have a gene to match 4. Newly formed sperm: seminiferous tubule S epididymis S ductus (vas) one found on the X chromosome. Thus, a male may inherit a recessive X deferens S ejaculatory duct (passing the seminal vesicles, prostate gland, trait and will exhibit it, while a female who inherits the same recessive trait and bulbourethral glands) S urethra. Ovulated egg: fallopian tube S uter- will not exhibit it if her second X chromosome has the dominant gene for the ine cavity S cervix S vagina trait. 5. (a) converts androgens to estrogens (b) tight junctions that prevent free 13. (a) Gamete—eggs and sperm. Germ cell—cell that will become a gamete. movement of substances between blood and seminiferous tubule lumen Zygote—formed from the fusion of egg and sperm; undergoes mitosis to (c) Sertoli cell protein secreted into seminiferous tubule lumen, where it become an embryo. In 8th week of pregnancy, embryo becomes a fetus. (b) binds and concentrates androgens (d) formed by the first meiotic division Coitus—intercourse. Erection—stiffening and enlargement of the penis. of a primary oocyte; disintegrates and has no function (e) lysosome-like Male orgasm—sperm move into the urethra during emission, then out of structure in the head of sperm; contains enzymes essential for fertilization the body in semen during ejaculation. Erogenous zones—portions of the body with receptors for sexually arousing stimuli. (c) Capacitation—sperm 6. (a) False. Some is produced in the adrenal glands of both sexes. (b) False. maturation necessary before it can fertilize an egg. Zona pellucida—protec- Both sexes produce them. (c) True. (d) False. High levels of late follicular tive glycoprotein coat around the ovum. Acrosomal reaction—enzymes estrogen help prepare the uterus for implantation of a fertilized ovum. (e) help sperm penetrate the zona pellucida. Cortical reaction—granules in egg True. cytoplasm release their contents at fertilization to change the egg membrane 7. A sperm-fluid mixture made mostly by the accessory glands. See Figure 26.7 f properties. (d) Puberty—time of sexually maturation. Menarche—the first for components. menstrual period. Menopause—female reproductive cycles cease. Andro- 8. The most effective contraception is abstinence. Least effective forms rely pause—male counterpart to menopause. on avoiding intercourse during times when the female thinks she might be 14. (a) FSH—stimulates gamete production in both sexes. (b) Inhibin— fertile. inhibits FSH secretion. (c) Activin—stimulates FSH secretion. (d)

940 Reproduction and Development

GnRH—stimulates release of FSH and LH. (e) LH—stimulates gonadal polar body chromosomes are retained, the embryo will have three copies of sex hormone production; in females, also necessary for gamete matura- a chromosome instead of just two. tion. (f) DHT—testosterone metabolite responsible for fetal development 18. If the unovulated cysts continue to secrete estrogen and do not develop into of male genitalia. (g) Estrogen—present in both sexes but dominant in corpora lutea, the uterine lining will continue to grow and the breasts will females; female gamete formation and some secondary characteristics. (h) develop, just as during pregnancy. Testosterone in males—gamete formation. Both sexes—some secondary sex 19. (a) male (b) nonfunctional testes (c) no ducts of either type (d) female traits such as hair growth. (i) Progesterone—females only; helps prepare the uterus for pregnancy. 20. During pregnancy the mother’s blood glucose is available to the fetus, which metabolizes the extra energy and gains weight. The fetus also up-regulates 15. The four phases are similar in both sexes. Excitement—penis and clitoris insulin secretion to handle the glucose coming across the placenta. After become erect due to increased blood flow. The vagina secretes fluids for birth, when insulin is still high but glucose drops to normal, the baby may lubrication. In male orgasm, ejaculation takes place, while in female orgasm become hypoglycemic. the uterus and vaginal walls contract. 16. (a) hCG—keeps the corpus luteum from dying. (b) LH—no direct role in Level Four Quantitative Problems pregnancy. (c) HPL—regulation of maternal metabolism during pregnancy. (d) Estrogen—breast development; negative feedback signal to prevent new 21. (a) Because it was being administered to the subjects. (b) Negative feedback follicles from developing. (e) Progesterone—maintenance of the uterine by testosterone. (c) Sperm production decreased in the A–B interval because lining; prevents uterine contractions; mammary gland development. (f) FSH and LH decreased. It increased toward the end of the B–C interval be- Relaxin—prevents uterine contractions. (g) Prolactin—PIH levels decrease cause FSH allowed sperm production to resume. Sperm production did not so that prolactin levels will increase, allowing milk production. increase significantly during the D–E interval.

Level Three Problem Solving 17. Normally after fertilization the second polar body, containing a haploid set of chromosomes, is released from the zygote. If all or some of the second

Photo Credits

CO: Image Courtesy of R&D Systems 26.14a: Densey Clyne/Photolibrary. 26.1: CNRI/Science Photo Library/Photo Researchers, Inc. 26

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