The Reproductive System: Part A

Home , Cervical canal, Crus of clitoris, Ejaculatory duct, Labia, Membranous urethra, Mesometrium

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PowerPoint® Lecture Slides Reproductive System prepared by Barbara Heard, Atlantic Cape Community • Primary sex organs (gonads) - testes College and ovaries – Produce gametes (sex cells ) – sperm & ova C H A P T E R 27 – Secrete steroid sex hormones • Androgens (males) • Estrogens and progesterone (females) The • Accessory reproductive organs - ducts, Reproductive glands, and external genitalia System: Part A

• Sex hormones play roles in • Testes (within scrotum) produce sperm – Development and function of reproductive • Sperm delivered to exterior through organs system of ducts – Sexual behavior and drives – Epididymis  ductus deferens  ejaculatory – Growth and development of many other duct  urethra organs and tissues

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Male Reproductive System Figure 27.1 Reproductive organs of the male, sagittal view.

• Accessory sex glands Ureter

– Seminal glands Urinary bladder Peritoneum Prostatic – Prostate Seminal gland urethra (vesicle) Pubis – Bulbo-urethral glands Ampulla of Intermediate ductus deferens part of the Ejaculatory duct urethra – Empty secretions into ducts during ejaculation Rectum Urogenital Prostate diaphragm Corpus Bulbo-urethral gland cavernosum Anus Corpus Bulb of penis spongiosum Spongy Ductus (vas) deferens Epididymis urethra Testis Glans penis Scrotum Prepuce (foreskin) External urethral orifice

The Scrotum The Scrotum

• Sac of skin and superficial fascia • Temperature kept constant by two sets of – Hangs outside abdominopelvic cavity muscles – Contains paired testes – Dartos muscle - smooth muscle; wrinkles • 3C lower than core body temperature scrotal skin; pulls scrotum close to body • Lower temperature necessary for sperm – Cremaster muscles - bands of skeletal production muscle that elevate testes

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Figure 27.2 Relationships of the testis to the scrotum and spermatic cord. The Testes

• Each surrounded by two tunics Urinary bladder – Tunica vaginalis – outer layer derived from peritoneum Superficial inguinal ring (end of inguinal canal) Testicular artery – Tunica albuginea – inner layer; fibrous Spermatic cord Ductus (vas) capsule deferens Penis Autonomic nerve fibers • Septa divide testis into ~250 lobules, each Septum of scrotum Pampiniform containing 1–4 seminiferous tubules - venous plexus Cremaster muscle Epididymis site of sperm production Tunica vaginalis External spermatic (from peritoneum) fascia Superficial fascia containing dartos Tunica albuginea Scrotum muscle of testis Skin Internal spermatic fascia © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc.

Seminiferous Tubules The Testes

• Interstitial endocrine cells in soft tissue • Blood supply surrounding seminiferous tubules – Testicular arteries arise from abdominal aorta • Produce androgens, e.g., testosterone – Testicular veins arise from pampiniform – Secrete it into interstitial fluid venous plexus surrounding each testicular artery • Cooler; absorb heat from testicular arteries • Keep testes cool • Spermatic cord encloses nerve fibers, blood vessels, and lymphatics that supply testes

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Figure 27.3a Structure of the testis. The Penis Spermatic cord

Blood vessels and nerves • Penis consists of – Root and shaft that ends in glans penis

Ductus (vas) – Prepuce, or foreskin—cuff of loose skin deferens Testis Head of epididymis covering glans Efferent ductule Seminiferous tubule – Crura Rete testis Lobule • Proximal ends of corpora cavernosa surrounded Straight tubule Septum by ischiocavernosus muscle; anchors penis to Tunica albuginea Body of epididymis pubic arch Tunica vaginalis Duct of epididymis Cavity of tunica vaginalis Tail of epididymis

Circumcision The Penis: Internally

• Surgical removal of foreskin • Spongy urethra and three cylindrical • 60% newborn boys in US circumcised bodies of erectile tissue (spongy network – 15% in other parts of world of connective tissue and smooth muscle – Some claim medically unnecessary with vascular spaces) – Studies show – Corpus spongiosum - surrounds urethra and expands to form glans and bulb • 60% reduction in HIV risk • Reduced risk for other reproductive system – Corpora cavernosa - paired dorsal erectile infections bodies • Erection - erectile tissue fills with blood, causing penis to enlarge and become rigid

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Figure 27.5 Male reproductive structures. The Male Duct System Ureter

Urinary bladder

Ampulla of ductus deferens • Ducts carry sperm from testes to body Seminal gland Prostate

Prostatic urethra Ejaculatory duct exterior Orifices of prostatic ducts Bulbo-urethral gland and duct Intermediate part of the urethra – Epididymis (membranous urethra) Urogenital diaphragm Bulb of penis Root of penis Crus of penis – Ductus deferens Bulbo-urethral duct opening Ductus deferens Corpora cavernosa – Ejaculatory duct Epididymis Corpus spongiosum Body (shaft) of penis Testis – Urethra Section of (b)

Spongy urethra

Glans penis Prepuce (foreskin)

External urethral orifice

Dorsal vessels Corpora cavernosa and nerves

Urethra Skin Tunica albuginea of erectile bodies Deep arteries Corpus spongiosum

Epididymis Ductus Deferens and Ejaculatory Duct

• Head - contains efferent ductules; superior • Ductus deferens (vas deferens) ~ 45 cm aspect of testis; body and tail on posterolateral – Passes through inguinal canal to pelvic cavity area of testis – Expands to form ampulla; joins duct of • Duct of the epididymis ~ 6 m in length seminal vesicle to form ejaculatory duct – Microvilli (stereocilia) absorb testicular fluid and pass nutrients to stored sperm • Smooth muscle in walls propels sperm • Nonmotile sperm enter, pass slowly through (~ from epididymis to urethra 20 days), become motile; can be stored several • Vasectomy - cutting and ligating ductus months deferens; nearly 100% effective form of • During ejaculation epididymis contracts, birth control expelling sperm into ductus deferens

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Urethra Figure 27.5 Male reproductive structures. Ureter

Urinary bladder

• Conveys both urine and semen (at Ampulla of ductus deferens Seminal gland Prostate

different times) Prostatic urethra Ejaculatory duct Orifices of prostatic ducts Bulbo-urethral gland and duct Intermediate part of the urethra • Has three regions (membranous urethra) Urogenital diaphragm Bulb of penis

Root of penis Crus of penis – Prostatic urethra – surrounded by prostate Bulbo-urethral duct opening Ductus deferens – Intermediate part of the urethra Corpora cavernosa Epididymis Corpus spongiosum Body (shaft) (membranous urethra) – in urogenital of penis Testis Section of (b) diaphragm Spongy urethra

– Spongy urethra – runs through penis; opens Glans penis Prepuce (foreskin) at external urethral orifice External urethral orifice Dorsal vessels Corpora cavernosa and nerves

Urethra Skin Tunica albuginea of erectile bodies Deep arteries Corpus spongiosum

The Male Accessory Glands Accessory Glands: Seminal Glands

• Paired seminal glands (seminal • On posterior bladder surface; smooth vesicles) muscle contracts during ejaculation • Paired bulbo-urethral glands • Produces viscous alkaline seminal fluid • Prostate – Fructose, citric acid, coagulating enzyme (vesiculase), and prostaglandins • Produce bulk of semen – Yellow pigment fluoresces with UV light – Remainder - sperm from testes – 70% volume of semen • Duct of seminal gland joins ductus deferens to form ejaculatory duct

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Accessory Glands: Prostate Prostate Disorders

• Encircles urethra inferior to bladder; size • Prostatitis – inflammatory disorders of peach pit; smooth muscle contracts – Bacterial infection; acute and chronic; treated during ejaculation with antibiotics • Secretes milky, slightly acid fluid • Benign prostatic hyperplasia – Contains citrate, enzymes, and prostate- – May be age-related; distorts urethra; treated specific antigen (PSA) with surgery, microwaves, drugs, balloon – Role in sperm activation compression, radio-frequency radiation – Enters prostatic urethra during ejaculation • 1/3 semen volume

Prostate Disorders Accessory Glands: Bulbo-Urethral Glands (Cowper's Glands) • Prostate cancer • Pea-sized glands inferior to prostate – Second most common cause of cancer death • Produce thick, clear mucus during sexual in males arousal – Digital exam screening, PSA levels – Lubricate glans penis • Biopsy if abnormal – Neutralize traces of acidic urine in urethra – Treated with surgery and sometimes radiation; castration; drugs – In clinical trials - cryosurgery, chemotherapy, ultrasound, proton beam therapy

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Figure 27.5 Male reproductive structures. Semen Ureter

Urinary bladder

Ampulla of ductus deferens • Milky-white mixture of sperm and Seminal gland Prostate accessory gland secretions Prostatic urethra Ejaculatory duct Orifices of prostatic ducts Bulbo-urethral gland and duct – 2–5 ml semen ejaculated, contains 20–150 Intermediate part of the urethra (membranous urethra) Urogenital diaphragm Bulb of penis million sperm/ml Root of penis Crus of penis Bulbo-urethral duct opening Ductus deferens • Contains fructose for ATP production; Corpora cavernosa Epididymis protects and activates sperm; facilitates Corpus spongiosum Body (shaft) of penis Testis Section of (b) sperm movement Spongy urethra • Alkaline  neutralizes acidity of male

Glans penis Prepuce (foreskin)

External urethral orifice urethra and female vagina  enhanced

Dorsal vessels Corpora cavernosa and nerves motility Urethra Skin Tunica albuginea of erectile bodies Deep arteries Corpus spongiosum

Semen Functions Male Sexual Response

• Prostaglandins decrease viscosity of mucus in • Erection cervix; stimulate reverse peristalsis in uterus – Arterioles normally constricted • Hormone relaxin, enzymes  sperm motility – Sexual excitement causes CNS activation of • Contains ATP for energy parasympathetic neurons • Suppresses female immune response –  nitric oxide (NO) release  local vascular • Antibacterial action smooth muscle relaxation • Clotting factors coagulate semen initially to –  arterioles dilate  corpora cavernosa prevent draining out; then liquefied by expands, retards venous drainage fibrinolysin  sperm begin journey –  engorgement of erectile tissues with blood –  enlargement and stiffening of penis

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Male Sexual Response Homeostatic Imbalance

• Ejaculation • Erectile dysfunction – Propulsion of semen from male duct system – Parasympathetic nerves of penis release too – Sympathetic spinal reflex little NO • Bladder sphincter muscle constricts, preventing – Causes – alcohol, drugs, hormones, blood expulsion of urine vessel or nervous system problems, • Ducts and accessory glands contract and empty incompetent venous valves fail to retain blood their contents in penis • Bulbospongiosus muscles undergo rapid series of – New drugs (Viagra, Cialis) potentiate existing contractions  expulsion of semen at ~ 500 cm/s (close to 11 mph) NO effects – Ejaculatory event – climax (orgasm)

Figure 27.6 Comparison of mitosis and meiosis in a mother cell with a diploid number (2n) of 4.

Mother cell Spermatogenesis (before chromosome replication)

Chromosome Chromosome replication replication

2n = 4

MITOSIS MEIOSIS

Tetrad formed by • Sperm (spermatozoa) production in Replicated synapsis of Prophase chromosome Prophase I replicated homologous seminiferous tubules chromosomes

Chromosomes Tetrads align randomly Metaphase align at the Metaphase I at the metaphase plate • Most body cells have 46 chromosomes - metaphase plate Sister chromatids separate during anaphase Homologous chromosomes separate but sister chromatids diploid chromosomal number (2n) remain together during anaphase I Daughter cells of Daughter cells – Two sets (23 pairs) of chromosomes mitosis of Meiosis I No further chromosomal 2n 2n replication; sister chromatids • One maternal, one paternal – homologous Meiosis II separate during anaphase II

chromosomes n n n n Daughter cells of meiosis II (usually gametes) – Gametes have 23 chromosomes - haploid MITOSIS MEIOSIS Number of One, consisting of prophase, metaphase, Two, each consisting of prophase, metaphase, anaphase, and telophase. divisions anaphase, and telophase. DNA replication does not occur between the two nuclear divisions.

Synapsis of Does not occur. Occurs during prophase I; tetrads form, allowing crossovers. chromosomal number (n) homologous chromosomes Daughter cell Two. Each diploid (2n) cell is identical to Four. Each haploid (n) cell contains half as many chromosomes as the number and the mother cell. mother cell and is genetically different from the mother cell. genetic • Only one member of homologous pair composition Roles For development of multicellular adult from Produces cells for reproduction (gametes). Introduces genetic variability in the body zygote. Produces cells for growth and tissue in the gametes and reduces chromosomal number by half so that when repair as multicellular adult develops. Ensures fertilization occurs, the normal diploid chromosomal number is restored genetic makeup of all body cells is constant. (in humans, 2n = 46).

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Figure 27.7 Meiosis.

Interphase cell MEIOSIS I Prophase I Spermatogenesis Nuclear Centromere Prophase events occur, as in mitosis. Additionally, Crossover synapsis occurs: Homologous chromosomes come Centriole envelope Spindle together along their length to form tetrads. During pairs synapsis, the “arms” of homologous chromatids wrap around each other, forming several crossovers. The Sister nonsister chromatids trade segments at points of chromatids crossover. Crossover is followed through the diagrams below. Chromatin Nuclear envelope fragments late 2n = 4 in prophase I

Interphase events As in mitosis, meiosis is preceded by DNA replication and other • Spermatogenic cells give rise to sperm Metaphase I preparations for cell division. The tetrads align randomly on the spindle equator in preparation for anaphase.

Tetrad – Mitosis of spermatogonia (stem cell) forms

Dyad Anaphase I Unlike anaphase of mitosis, the centromeres do not separate during anaphase I of meiosis, so the sister chromatids (dyads) remain firmly attached. However, the two spermatocytes homologous chromosomes do separate from each other and the dyads move toward opposite poles of the cell.

Chromosomes uncoil Telophase I The nuclear membranes re-form around the – Meiosis Nuclear chromosomal masses, the spindle breaks down, and envelopes the chromatin reappears as telophase and cytokinesis re-form end. The 2 daughter cells (now haploid) enter a second interphase-like period, called interkinesis, before Cleavage meiosis II occurs. There is no second replication of DNA furrow • Spermatocytes  secondary spermatocytes  before meiosis II. MEIOSIS II spermatids Prophase II Meiosis II begins with the products of meiosis I (2 haploid daughter cells) and undergoes a mitosis-like nuclear division process referred to as the equational – Spermiogenesis division of meiosis. Metaphase II • Spermatids become sperm

Anaphase II After progressing through the phases of meiosis and cytokinesis, the product is 4 haploid cells, each genetically different from the original Telophase II mother cell. (During human and cytokinesis spermatogenesis, the daughter cells remain interconnected by cytoplasmic extensions during the meiotic phases.) Products of meiosis: haploid daughter cells

Figure 27.8a Spermatogenesis. Figure 27.8c Spermatogenesis. Tight junction between sustentocytes

Spermatogonium Cytoplasm of (stem cell) adjacent Sustentocyte sustentocytes cell nucleus Basal lamina

Type A daughter cell remains at basal lamina as a precursor cell

Type B daughter cell Basal Basal

Primary compartment spermatocyte

Secondary spermatocytes Early spermatids Late spermatids

Cytoplasmic bridge Adluminal Adluminal Lumen compartment of seminiferous Spermatozoa tubule

Scanning electron micrograph of a

cross-sectional view of a seminiferous A portion of the seminiferous tublule wall, showing the x spermatogenic cells surrounded by sustentocytes (colored gold) © 2013 Pearson Education, Inc. tubule (165 ) © 2013 Pearson Education, Inc.

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Mitosis of Spermatogonia Mitosis of Spermatogonia

• Spermatogenesis begins at puberty • Type A cells maintain germ cell line at • Spermatogonia basal lamina – Stem cells in contact with epithelial basal • Type B cells move toward lumen and lamina develop into primary spermatocytes – Each mitotic division  one type A daughter cell and one type B daughter cell

Figure 27.8b Spermatogenesis. Figure 27.9 Spermiogenesis: transformation of a spermatid into a functional sperm. Slide 1 Basal lamina

Spermatogonium 2n 2n Type A daughter cell Approximately 24 days (stem cell) remains at basal lamina Mitosis as a precursor cell Golgi apparatus 2n Type B daughter cell Acrosomal Mitochondria Growth vesicle Enters meiosis I and Acrosome moves to Primary adluminal 2n Nucleus compartment spermatocyte Meiosis I completed n n Secondary 1 2 spermatocytes Spermatid Centrioles Meiosis ll nucleus Microtubules Midpiece Head Meiosis (early Meiosis 3 Flagellum

spermatogenesis) n n n n Early spermatids Excess cytoplasm

n n n n Late spermatids Spermatogenesis

4 Tail 5 n n n n

spermatogenesis) Spermatozoa

Spermiogenesis (late (late Spermiogenesis 6 7

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Spermatogenesis Homeostatic Imbalance

• Takes 64 – 72 days if conditions • Infertility hospitable – Gradual decline in male fertility past 50 years • Pressure of testicular fluid pushes – Xenobiotics (alien molecules) may be cause immotile sperm into epididymis  motility • Environmental toxins, PVCs, phthalates, pesticides, herbicides, compounds with estrogenic and fertilizing power effects, antibiotics, radiation, lead, marijuana – Also, lack of selenium, excessive alcohol, lack of specific Ca2+ channel, anatomical obstructions, hormonal imbalances, oxidative stress, fevers, hot tubs

Hormonal Regulation of Male Reproductive HPG Axis Function • Sequence of hormonal regulatory events • Testosterone  sex organ maturation, involving hypothalamus, anterior pituitary development/maintenance secondary sex gland, and testes characteristics, libido – Hypothalamic-pituitary-gonadal (HPG) axis • Rising testosterone levels  feedback – Regulates production of gametes and sex inhibition on hypothalamus to inhibit GnRH hormones through 3 interacting sets of and on pituitary to inhibit gonadotropin hormones release • GnRH indirectly stimulates testes via FSH & LH • FSH & LH directly stimulate testes • Inhibin (released when sperm count high) – • Testosterone & inhibin – negative feedback on inhibits GnRH and FSH release hypothalamus and anterior pituitary

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Figure 27.10 Hormonal regulation of testicular function, the hypothalamic-pituitary-gonadal (HPG) axis. Slide 1 Figure 27.11 Plasma testosterone and sperm production levels versus age in male humans.

1 Adult

GnRH Fertilization Birth 100 Anterior Via portal Puberty pituitary blood

7 6

Inhibin 2 FSH LH Interstitial 50 4 endocrine 3 cells Testosterone Somatic and Sustentocyte 5 psychological effects at other body sites; Plasma testosteronelevel Spermatogenic maintenance cells of secondary sex

characteristics Spermproduction (% of maximal) 0 3 6 9 1 10 20 60

Female Reproductive Anatomy Female Reproductive Anatomy

• Ovaries - female gonads • Internal genitalia – in pelvic cavity – Produce female gametes (ova) – Ovaries – Secrete female sex hormones, estrogen – Uterine tubes (estradiol, estrone, estriol) and progesterone – Uterus • Accessory ducts include – Vagina – Uterine tubes • External genitalia – Uterus – External sex organs – Vagina

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Figure 27.12 Internal organs of the female reproductive system, midsagittal section. Figure 27.14 Internal reproductive organs of a female, posterior view.

Suspensory Suspensory ligament ligament of ovary of ovary Uterine (fallopian) tube Ovarian Infundibulum blood Fundus of uterus Lumen (cavity) Uterine tube vessels of uterus Uterine tube Ovary Broad ligament Ovary • Ampulla Fimbriae • Isthmus Peritoneum • Mesosalpinx Uterus • Mesovarium • Infundibulum Uterosacral • Fimbriae Round ligament • Mesometrium ligament Vesicouterine Perimetrium pouch Rectouterine Urinary bladder Ovarian Round ligament of uterus pouch Pubic symphysis ligament Wall of uterus Rectum Mons pubis Posterior fornix Body of uterus • Endometrium • Myometrium Cervix Urethra Ureter • Perimetrium Anterior fornix Clitoris Uterine blood vessels • Internal os Vagina External urethral Isthmus • Cervical canal Anus orifice Uterosacral ligament • External os Urogenital diaphragm Hymen Cardinal (lateral cervical) Greater vestibular Labium minus ligament Lateral fornix gland Labium majus Vagina Cervix

Figure 27.13 Photomicrograph of a mammalian ovary showing follicles in different developmental phases. Female Duct System

Germinal Tunica Cortex Medulla epithelium albuginea • Ducts have no contact with ovary – Oocyte cast into peritoneal cavity; some lost there • Uterine (fallopian) tubes or oviducts • Uterus

Primary follicles • Vagina

Secondary follicle Antrum of a vesicular (antral) follicle

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Homeostatic Imbalance Homeostatic Imbalance

• Ectopic pregnancy • Cervical cancer – Oocyte fertilized in peritoneal cavity or distal – 450,000 women worldwide each year – killing uterine tube begins developing there half • Normally abort naturally with substantial bleeding – Most common between 30 – 50 • Pelvic inflammatory disease (PID) – Risks – frequent cervical inflammations, STIs, – Spread of infection from reproductive tract to multiple pregnancies peritoneal cavity – Papanicolaou (Pap) smear for detection • May cause scar tissue  infertility • Every two years 21 – 30; every year > 30; discontinue at 65 if negative for 10 years

Homeostatic Imbalance Vagina

• Pap smear results inconclusive • Layers of wall – Test for human papillomavirus – cause of – Fibroelastic adventitia most cervical cancers – Smooth muscle muscularis – Stratified squamous mucosa with rugae • Gardasil – three-dose vaccine; protects • Dendritic cells in mucosa may provide route for against HPV HIV transmission – Recommended for 11- and 12-year-old girls • Mucosa near vaginal orifice forms incomplete partition called hymen – ruptures with intercourse • Vaginal fornix - upper end of vagina surrounding cervix

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Figure 27.16a The external genitalia (vulva) of the female. External Genitalia (Vulva or Pudendum)

Mons Labia pubis majora • Mons pubis - fatty area overlying pubic Prepuce of clitoris Labia symphysis minora Clitoris • Labia majora - hair-covered, fatty skin (glans) External Vestibule urethral folds orifice – Counterpart of male scrotum Hymen (ruptured) • Labia minora - skin folds lying within labia Vaginal Anus orifice majora – Join at posterior end of vestibule  fourchette Opening of the duct – Vestibule - recess within labia minora of the greater vestibular gland

External Genitalia External Genitalia

• Greater vestibular glands • Clitoris – anterior to vestibule – Flank vaginal opening – Glans of the clitoris - exposed portion – Homologous to bulbo-urethral glands – Prepuce of the clitoris – hoods glans – Release mucus into vestibule for lubrication – Counterpart of penis • Perineum – Diamond-shaped region between pubic arch and coccyx – Bordered by ischial tuberosities laterally

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Figure 27.16b The external genitalia (vulva) of the female. Mammary Glands Clitoris Labia minora Labia majora • Modified sweat glands consisting of 15–25 Anus lobes Pubic symphysis Inferior Body of clitoris, ramus containing • Function in milk production of pubis corpora cavernosa • Areola - pigmented skin surrounding Clitoris (glans) Crus of clitoris nipple

External urethral orifice • Suspensory ligaments – attach breast to Vaginal orifice underlying muscle Greater vestibular • Lobules within lobes contain glandular gland Bulb of vestibule alveoli that produce milk Fourchette

Mammary Glands Figure 27.17 Structure of lactating mammary glands.

First rib

• Milk  lactiferous ducts  lactiferous Skin (cut) sinuses  open to outside at nipple Pectoralis major muscle Suspensory ligament • Breast size due to amount of fat deposits Adipose tissue Lobe Areola Nipple

Opening of lactiferous duct

Lactiferous sinus

Lactiferous duct Lobule containing alveoli

Hypodermis (superficial fascia)

Intercostal muscles

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Breast Cancer Breast Cancer

• Invasive breast cancer most common • Usually arises from epithelial cells of malignancy, second most common cause smallest ducts; eventually metastasize of cancer death in U.S. women • Risk factors include • 13% will develop condition – Early onset of menstruation and late menopause – No pregnancies or first pregnancy late in life – No or short periods of breast feeding – Family history of breast cancer • 70% of women with breast cancer have no known risk factors

Breast Cancer Breast Cancer: Treatment

• 10% due to hereditary defects, including • Radical mastectomy – removes breast, mutations to genes BRCA1 and BRCA2 all underlying muscles, fascia, associated – 50 – 80% develop breast cancer lymph nodes – Greater risk of ovarian cancer as well • Lumpectomy – excises only cancerous lump • Simple mastectomy – removes only breast tissue, sometimes some axillary lymph nodes • Some have breast reconstruction

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Figure 27.18 Mammograms. Physiology of the Female Reproductive System • Always assumed females total supply of eggs determined at birth Malignancy • New evidence stem cells can arise from epithelial cells at ovary surface • May overturn previous assumption

Mammogram procedure Film of normal breast Film of breast with tumor

Figure 27.19 Events of oogenesis. Meiotic events Follicle development Comparison of Oogenesis and in ovary Before birth 2n Oogonium (stem cell) Follicle cells Spermatogenesis Mitosis Oocyte 2n Primary oocyte Primordial follicle • Spermatogenesis  4 viable sperm

Infancy and 2n Primary oocyte Primordial follicle childhood (arrested in prophase I; (ovary functionally present at birth) • Spermatogenesis – error rate of 3-4% inactive)

Each month from • Oogenesis  1 viable gamete; 3 polar puberty to menopause Primary follicle

2n Primary oocyte (still arrested in prophase I) bodies Secondary follicle

Spindle Vesicular (antral) • Oogenesis – error rate of 20% follicle

Meiosis I (completed by one primary oocyte each • Unequal divisions ensure oocyte has month in response to LH surge) Secondary oocyte (arrested in metaphase II) First polar body n ample nutrients for 6-7 day journey to

Ovulation Meiosis II of polar body uterus (may or may not occur) Sperm Ovulated secondary oocyte Meiosis II completed In absence of fertilization, (only if sperm • Polar bodies degenerate and die ruptured follicle becomes n n n n penetrates a corpus luteum and Polar bodies oocyte) ultimately degenerates. (all polar bodies Second Ovum degenerate) polar body Degenerating corpus luteum © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc.

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Ovarian Cycle Ovarian Cycle

• Monthly series of events associated with • Only 10 – 15% women have 28-day cycle maturation of egg • Follicular phase varies • Two consecutive phases (in 28-day cycle) • Luteal phase constant – always 14 days – Follicular phase - period of follicle growth from ovulation to end of cycle (days 1–14) – Ovulation occurs midcycle – Luteal phase - period of corpus luteum activity (days 14–28)

Figure 27.20 Schematic and microscopic views of the ovarian cycle: development and fate of ovarian Slide 1 follicles. PowerPoint® Lecture Slides prepared by Barbara Heard, Atlantic Cape Community College Theca 1 Primordial 2 Primary folliculi follicles follicle 3a Secondary Theca folliculi follicle 3b 3a 3b Late secondary Forming 2 Primary follicle antrum 7 oocyte Zona pellucida C H A P T E R Antrum 27 Secondary 4 oocyte Secondar 5 6 y 6 oocyte Corona Zona radiata pellucida The

Antrum Reproductive System: Part C 6 Corpus luteum 5 Follicle ruptures; 4 Mature vesicular follicle (forms from ruptured carries out meiosis I; ready secondary oocyte © Annie Leibovitz/Contact Press Images © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc. follicle) ovulated to be ovulated

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Figure 27.21 Regulation of the ovarian cycle. Slide 1 Figure 27.22a Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus. Hypothalamus Hypothalamus GnRH 4 Positive 4 feedback exerted GnRH by large in Travels via estrogen output 6 portal blood by maturing follicle. 1 LH

Anterior pituitary 1 4 Progesterone LH surge Estrogens Inhibin FSH LH Ruptured 5 2 2 follicle 6 Thecal cells FSH 3 Slightly 2 Androgens hormone Plasma level elevated 5 estrogen and Granulosa rising inhibin cells levels inhibit 2 Inhibin Mature vesicular FSH Convert androgens follicle Ovulated Corpus luteum secretion. to estrogens secondary Fluctuation of gonadotropin levels: Fluctuating levels of pituitary 2 oocyte gonadotropins (follicle-stimulating hormone and luteinizing hormone) Estrogens in the blood regulate the events of the ovarian cycle. Early and Late follicular and midfollicular phases luteal phases Stimulates © 2013 Pearson Education, Inc. Inhibits © 2013 Pearson Education, Inc.

Figure 27.22b Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus. The Uterine (Menstrual) Cycle

• Cyclic changes in endometrium in response to fluctuating ovarian hormone levels

Primary Secondary Vesicular Ovulation Corpus Degenerating • Three phases follicle follicle follicle luteum corpus luteum – Days 1–5 - menstrual phase – Days 6–14 - proliferative (preovulatory) phase Follicular Ovulation Luteal – Days 15–28 - secretory (postovulatory) phase phase (Day 14) phase Ovarian cycle: Structural changes in the ovarian follicles during the (constant 14-day length) ovarian cycle are correlated with (d) changes in the endometrium of the uterus during the uterine cycle.

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Uterine Cycle Uterine Cycle

• Menstrual phase (Days 1 - 5) • Proliferative phase (Days 6 - 14) – Ovarian hormones at lowest levels – Rising estrogen levels prompt generation of – Gonadotropins beginning to rise new stratum functionalis layer; increased – Stratum functionalis shed; menstrual flow synthesis of progesterone receptors in (blood and tissue) 3 - 5 days endometrium; glands enlarge and spiral arteries increase in number – By day 5 growing ovarian follicles produce more estrogen – Normally thick, sticky cervical mucus thins in response to rising estrogen (allows sperm passage) – Ovulation occurs at end of proliferative phase

Figure 27.22c Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus. Figure 27.22d Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus.

Endometrial Blood vessels glands

Menstrual flow Functional layer Estrogens Basal layer Days 1 5 10 15 20 25 28 Menstrual Proliferative Secretory Progesterone phase phase phase

Plasma hormone Plasma level The three phases of the uterine cycle: Fluctuation of ovarian hormone levels: Fluctuating levels of ovarian • Menstrual: The functional layer of the endometrium is shed. hormones (estrogens and progesterone) cause the endometrial changes • Proliferative: The functional layer of the endometrium is rebuilt. of the uterine cycle. The high estrogen levels are also responsible for the • Secretory: Begins immediately after ovulation. Enrichment of the blood LH/FSH surge in (a). supply and glandular secretion of nutrients prepare the endometrium to receive an embryo. Both the menstrual and proliferative phases occur before ovulation, and together they correspond to the follicular phase of the ovarian cycle. The secretory phase corresponds in time to the luteal phase of the ovarian cycle.

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Effects of Estrogens

• Promote oogenesis and follicle growth in ovary • Exert anabolic effects on female reproductive tract • Support rapid but short-lived growth spurt at puberty

Effects of Estrogens Effects of Estrogens

• Induce secondary sex characteristics • Metabolic effects (not true secondary sex – Growth of breasts characteristics) – Increased deposit of subcutaneous fat (hips – Maintain low total blood cholesterol and high and breasts) HDL levels – Widening and lightening of pelvis – Facilitate calcium uptake

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Effects of Progesterone Sexually Transmitted Infections (STIs)

• Progesterone works with estrogen to • Also called sexually transmitted diseases establish and regulate uterine cycle (STDs) or venereal diseases (VDs) • Promotes changes in cervical mucus • U.S. – highest rates of infection among • Effects of placental progesterone during developed countries pregnancy • Latex condoms help prevent spread – Inhibits uterine motility • Single most important cause of – Helps prepare breasts for lactation reproductive disorders

Gonorrhea Gonorrhea

• Commonly called "the clap" • Signs and symptoms • Bacterial infection of mucosae of – Males reproductive and urinary tracts • Urethritis, painful urination, discharge of pus – Females • Spread by contact with genital, anal, and • 20% display no signs or symptoms pharyngeal mucosae • Abdominal discomfort, vaginal discharge, or abnormal uterine bleeding • Number of cases in U.S. declining • Can result in pelvic inflammatory disease and sterility • Treatment - antibiotics, but resistant strains becoming prevalent

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Syphilis Syphilis

• Bacterial infection transmitted sexually or • If untreated, secondary signs appear contracted congenitally several weeks later for 3–12 weeks, then – Infected fetuses stillborn or die shortly after disappear birth – Pink skin rash, fever, and joint pain • Infection asymptomatic for 2–3 weeks • Latent period may or may not progress to • Painless chancre appears at site of tertiary syphilis, characterized by gummas infection; disappears in few weeks (lesions of CNS, blood vessels, bones, and skin) • Treatment - penicillin

Chlamydia Trichomoniasis

• Most common bacterial STI in United States • Most common curable STI in active young • Responsible for 25–50% of all diagnosed cases women in U.S. of pelvic inflammatory disease • Symptoms - urethritis; penile and vaginal • Parasitic infection; easily, inexpensively discharges; abdominal, rectal, or testicular pain; treated painful intercourse; irregular menses • Yellow-green vaginal discharge with strong • Can cause arthritis and urinary tract infections in odor; some symptomless men; sterility in women; newborns contract in birth canal  trachoma (painful eye infection), respiratory tract inflammation • Treatment - tetracycline

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Viral Infections Viral Infections

• Genital warts • Genital herpes – Caused by human papillomavirus (HPV) – Caused by herpes simplex virus 2 – Second most common STI in United States – Characterized by latent periods and flare-ups – Increased risk of cancers in infected body • Congenital herpes can cause malformations of regions fetus • Linked to 80% cases of invasive cervical cancer; – Treatment - acyclovir and other antiviral drugs most strains do not cause cancer – Treatment difficult; controversial

Figure 27.24a Development of homologous structures of the external genitalia in both sexes. Figure 27.24b Development of homologous structures of the external genitalia in both sexes. Approximately 5 weeks

Glans penis

Labioscrotal Urethral folds Genital swellings (scrotum) Urethral fold tubercle

Anus Labioscrotal Anus swelling

Tail (cut) Urethral groove Glans penis

Penis

Scrotum Sexually indifferent stage Anus

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Figure 27.24c Development of homologous structures of the external genitalia in both sexes.

Approximately 5 weeks Development Aspects: Descent of the Glans clitoris Gonads Urogenital Labioscrotal sinus swellings • About two months before birth (labia majora) Urethral folds – Testosterone stimulates migration of testes Anus (labia minora) toward scrotum • Gubernaculum - fibrous cord from each testis to scrotum or from ovary to labium majus; guides descent Glans clitoris

Labia majora • Ovaries also descend, but stopped by broad ligament at pelvic brim

Labia Anus minora

Figure 27.23 Development of the internal reproductive organs.

Mesonephros Mesonephric (Wolffian) duct

Gonadal ridge Paramesonephric (Müllerian) duct

Metanephros (kidney) Cloaca

5- to 6-week embryo: sexually indifferent stage Testes Efferent ductules Ovaries

Epididymis Paramesonephric duct forming the uterine tube Paramesonephric duct (degenerating) Mesonephric duct (degenerating) Mesonephric duct forming the ductus deferens Fused Urinary bladder paramesonephric ducts forming the uterus Seminal gland Urinary bladder (moved aside)

Urogenital sinus Urogenital sinus forming the urethra forming the urethra and lower vagina

7- to 8-week male 8- to 9-week female

Urinary bladder Uterine tube

Seminal gland Ovary Prostate Bulbo-urethral gland Uterus

Ductus deferens

Urethra Urinary bladder (moved aside) Efferent ductules Vagina Epididymis Urethra Testis Hymen Penis Vestibule

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Development Aspects: Puberty Menopause

• FSH and LH elevated at birth but drop and • Has occurred when menses have ceased remain low during prepubertal years for an entire year • Reproductive organs grow to adult size • No equivalent to menopause in males and become functional – puberty – Males continue to produce sperm well into • Occurs in response to rising levels of eighth decade of life, though numbers and gonadal hormones motility decrease • Secondary sex characteristics appear • Earliest time that reproduction is possible

Menopause Menopause

• Declining estrogen levels  • Treatment with estrogen-progesterone – Atrophy of reproductive organs and breasts preparations given for years – Irritability and depression in some – Women's Health Initiative research reported – Hot flashes as skin blood vessels undergo increased risk of heart disease (51%), intense vasodilation invasive breast cancer (24%), stroke (31%), dementia (risk doubled) – Gradual thinning of skin and bone loss – Smallest does for shortest time alright to – Increased total blood cholesterol levels and reduce symptoms if no breast cancer or falling HDL mutated BRCA gene

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Sperm

• Major regions – Head - genetic region; nucleus and helmetlike acrosome containing hydrolytic enzymes that enable sperm to penetrate egg – Midpiece - metabolic region; mitochondria  ATP to move tail – Tail - locomotor region; flagellum

Role of Sustentocytes Mechanism and Effects of Testosterone Activity • Large supporting cells (Sertoli cells) • Testosterone – Extend through wall of tubule and surround – Synthesized from cholesterol developing cells – Transformed to exert its effects on some – Provide nutrients and signals to dividing cells target cells – Move cells along to lumen • Dihydrotestosterone (DHT) in prostate – Secrete testicular fluid into lumen for sperm • Estradiol in some neurons in brain transport – Phagocytize faulty germ cells and excess cytoplasm – Produce chemical mediators to regulate spermatogenesis

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Ovaries Breast Cancer: Diagnosis

• Held in place by several ligaments • Early detection via self-examination and – Ovarian ligament - anchors ovary medially to mammography uterus – X-ray examination – Suspensory ligament - anchors ovary – American Cancer Society recommends laterally to pelvic wall screening every year for women 40 and over – Mesovarium - suspends ovary – U.S. Prevention Services Task Force on • Suspensory ligament and mesovarium Breast Cancer Screening recommends 50 part of broad ligament – supports uterine and over tubes, uterus, and vagina

Breast Cancer: Treatment Developmental Aspects: Determination of Genetic Sex • Treatment depends upon characteristics of • Of 46 chromosomes in fertilized egg, two lesion (one pair) are sex chromosomes – Radiation; chemotherapy; surgery, often followed by radiation or chemotherapy to • Two sex chromosomes – X chromosome destroy stray cells (large); Y chromosome (quite small) – Drugs for estrogen-responsive cancers • Females are XX; each ovum always has • Trastuzumab – for aggressive cancer cells an X chromosome • Tamoxifen – improves outcome for premenopausal women with early- or late-stage • Males are XY, so ~50% of sperm contain • Letrozole – reduces recurrence X, ~50% contain Y

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Developmental Aspects: Determination of Developmental Aspects: Sexual Genetic Sex Differentiation • X egg + X sperm  XX (female offspring) • Sexually indifferent stage • X egg + Y sperm  XY (male offspring) – Gonads begin development in fifth week as gonadal ridges • The SRY gene on Y chromosome initiates – Paramesonephric (Müllerian) ducts (future female testes development and maleness ducts) form lateral to mesonephric (Wolffian) ducts (future male ducts); sexually indifferent stage - embryo could develop into male or female – Primordial germ cells migrate to gonadal ridges to provide germ cells destined to become spermatogonia or oogonia • Gonads begin development in seventh week in males, eighth week in females

Developmental Aspects: Development of External Genitalia • Genital tubercle  penis of male; clitoris of female • Urethral fold  spongy urethra of male; labia minora of female • Labioscrotal swellings  scrotum of male: labia majora of female • If testosterone absent, all embryos develop into females