Principles of Reproductive Biology and Development CONTENTS
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chapter 3 Principles of Reproductive Biology and Development CONTENTS Page Introduction . 43 Measurement of Reproductive Function: Relation to Workplace Hazards . 44 Normal Reproductive Biology and Development . 44 Hormonal Control Mechanisms . 44 Male Reproductive Function . 46 Female Reproductive Function . 48 Embryogenesis and Fetal Growth . 49 The Pregnant Woman . 49 Coping with Pregnancy Loss. 52 Lactation . 53 Sexual Development: Puberty . 53 Abnormal Development . 54 Historical Perspective. ., . 54 Terminology . 55 Mutagens . 56 Impaired Embryogenesis and Fetal Growth . 56 Mechanisms of Action of Reproductive and Developmental Toxicants . 57 Reproductive Dysfunction in the Population as a while . 59 Summary and Conclusions . 61 Chapter 3 References . 62 List of Tables Table No. Page 3-1.Measures of Reproductive Function Readily Obtainable Prior to Fertilization. 4S 3-2. Measures of Reproductive Function Readily Obtainable After Fertilization . 45 3-3. Stages of Embryonic and Fetal Development . 51 3-4. Principles of Teratogenesis and Timing of Embryonic and Fetal Toxicity . 57 List of Figures Figure Ale. Page 3-1.The Male Reproductive System . 47 3-2. Relation Between Oocyte Number and Age in Women.... 48 3-3,The Female Reproductive System . so 3-4.Relation Between Age, Oocyte Number, and Menopause . 51 3-5. Embryogenesis and Fetal Growth: Three Trimesters of Gestation . ., .. ...,., . 52 3-6. The Percentage of Normal Women Who Conceive per Menstrual Cycle and the Outcome of the Pregnancies. , . S3 3-7. Percentage of Surviving and Lost Human Embryos and Fetuses at Different Stages of Pregnancy. 54 3-8.Mechanisms of Action of Reproductive Toxins . 58 Chapter 3 Principles of Reproductive Biology and Development INTRODUCTION Normal reproductive function comes about only The significance of some aspects of reproduc- as a consequence of interactions among multiple tive function not overtly related to fertility is often physiological systems. In the narrowest sense, re- underestimated; because they are held to be production is the union of sperm and ovum to strictly private matters, many of these subjects form a new biological entity. Yet the union of ga- tend to go undiscussed. In fact, an individual’s re- metes is merely a signal event in the continuum productive function and, should it occur, repro- of physiological processes comprising normal re- ductive dysfunction, can be of extraordinary per- productive function, Prior to fertilization, for ex- sonal importance. Impotence, menstrual pain, and ample, the maturation of sperm and egg depends loss of libido exemplify instances of reproductive on the coordinated secretion of multiple hor- dysfunction that can have substantial impact on mones. At coitus, synchronized neural reflexes individual well-being and human relationships. and appropriate reproductive behaviors are re- Concern about reproductive processes is not quired to bring gametes together. After concep- limited to the brief periods in an individual’s life- tion, embryonic growth depends on the integrity time during which reproduction may actually oc- of the zygote and a remodeling of the maternal cur. Reproductive function is an integral part of circulatory system. The later growth and devel- everyday human health and well-being. Before, opment of the offspring are a function of both during, and after the childbearing years, repro- prenatal and postnatal nutrition. ductive hormones may act, for example, on such For purposes of this report, reproductive variables as resistance to heart disease and can- function is used in the broadest sense possible. cer, immune function, complexion, bone mineral It encompasses: content, and feeling and mood. Threats to repro- ductive function can take place at nearly any point ● the functional and structural integrity of the during an individual’s lifespan. In fact, the most sperm and ova; insidious hazards to reproductive function may ● differentiation and development of the inter- be those whose immediate effects are apparently nal and external reproductive organs and en- benign, but whose ill effects surface at a later docrine glands; date. ● activation of the adult reproductive system at puberty; Viewed from this perspective, the bounds of ● senescence of the adult reproductive system typical reproductive function and the task of (e.g., menopause); defining atypical reproductive function seem im- ● behaviors associated with or subserving re- possibly broad in scope. Yet, by using an array production (e.g., libido); of well-defined endpoints, it is possible to assess ● maternal and paternal prenatal events; human reproductive function in both a qualita- ● embryonic and fetal events (e.g., organo- tive and a quantitative manner. genesis); ● maternal postnatal events (e.g., lactation); and ● child health and development. 43 44 . Reproductive Health Hazards in the Workplace MEASUREMENT OF REPRODUCTIVE FUNCTION: RELATION TO WORKPLACE HAZARDS For the couple desiring to reproduce, it may be Table 3-1 lists measures by which reproductive argued that the only meaningful index of repro- function may be assessed in adult men and wom- ductive function is the ability to produce a healthy en. The measures listed are limited to those that baby when they wish to do so. At any given time, are readily observable in a relatively noninvasive the couple either can, or cannot, procreate. But, fashion. In order to have broad applicability in for the purposes of this report, this final common a workplace or outpatient setting, such measures denominator of successful procreation must be are obtainable by one or more of the following dissected into numerous constituent factors in or- means: der to: 1) examine the nature of reproductive ● a detailed patient history, function and dysfunction, and 2) relate reproduc- ● a physical examination, tive dysfunction to a potential workplace hazard. ● blood samples, Multiple endpoints of reproductive function fur- ● semen samplesl or ther serve to define the reproductive status and . urine samples. physiological well-being of the majority of the pop- ulation who are, at any given time, not pro- Table 3-1 illustrates the disparity between the creating, ease with which male and female reproductive parameters can be assessed. That is, sperm are Endpoints used for measuring reproductive readily accessible, while eggs are not Table 3-2 function may be divided into two groups: 1) those lists measures by which reproductive function serving as indices of reproductive function inde- may be assessed in the adult woman and her off- pendent of fertilization, and 2) those serving as spring during pregnancy and after birth. Again, such indices after fertilization. There are close the measures listed are limited to those readily parallels between male and female reproductive obtainable in the relatively noninvasive fashion processes up to the point at which sperm and egg just described. A comprehensive discussion of the mature. Thereafter, most of the reproductive methods used to assess reproductive function, in- processes related to procreation occur in the fe- cluding more sophisticated methods than those male, as the fetal-placental-maternal system ex- listed in these tables, appears in chapter 5. hibits many stages without counterpart in the male. NORMAL REPRODUCTIVE BIOLOGY AND DEVELOPMENT Hormonal Control Mechanisms a consequence, this vital reproductive hormone— a telling indicator of reproductive function—is In both men and women, the hypothalamus, an possible but difficult to detect in peripheral blood area at the base of the brain, serves as a funda- circulation. mental neural regulator of the body’s reproduc- tive function. It receives neural and hormonal in- LHRH acts on cells of the anterior pituitary put from the brain and endocrine glands and re- gland to promote secretion of two hormones, lu - sponds to these stimuli by secreting luteinizing teinizing hormone (LH) and follicle-stimulating hormone-releasing hormone (LHRH) and other hormone (FSH). LH and FSH, known as gonado- hormones. The hypothalamus releases LHRH into tropin, direct hormone and gamete production tiny blood vessels which surround the pituitary by the testes and ovaries. As the gonads release gland, With a target so nearby, LHRH is released hormones in response to stimulation by LH and in minute amounts and breaks down quickly. As FSH, these gonadal hormones act at the hypothal- Ch. 3—Principles of Reproductive Biology and Development ● 45 Table 3-1.—Measures of Reproductive Function Readily Obtainable Prior to Fertilization Affected individual Endpoint Male (Both) Female Sexual function: Erection Libido Ejaculation Behavior Endocrine system: Luteinizing hormone Cervical mucus Follicle-stimulating quality hormone Steroid hormones (androgens, estrogens, and progestins) Germ cells: Sperm number Sperm motility Sperm shape (morphology) Chromosomal integrity Fertilizing ability Fecundity: Testicular integrity Integrity of external Ovarian integrity Semen quality genitalia Blockage of oviduct Menstrual regularity Amenorrhea Anovulatory cycles Secondary sexual Breast development characteristics: Facial and axillary hair growth Sebaceous glands Reproductive lifespan: Age at puberty Age at menopause SOURCE: Office of Technology Assessment. Table 3.2.—Measures of Reproductive Function Readily Obtainable After Fertilization Affected individual Endpoint Female (Both) Offspring Endocrine system: Human chorionic gonadotropin Steroid hormones, especially progesterone Health during pregnancy: Hemorrhage