1 The Reproductive System: Part C27 The Reproductive System: Part C

2 Establishing the Ovarian CycleDuring childhood, ovaries grow and secrete small amounts of estrogens that inhibit hypothalamic release of GnRH As puberty nears, GnRH released; FSH and LH released by pituitary, and act on ovaries These events continue until an adult cyclic pattern achieved and menarche occurs © 2013 Pearson Education, Inc.

3 Hormonal Regulation of the Ovarian CycleHormone interaction produces cyclic events in ovaries Gonadotropin-releasing hormone (GnRH) Pituitary gonadotropins Ovarian estrogen Ovarian progesterone Onset of puberty linked to amount of adipose tissue via hormone leptin © 2013 Pearson Education, Inc.

4 Establishing the Ovarian CycleDuring childhood, until puberty Ovaries secrete small amounts of estrogens Estrogen inhibits release of GnRH If leptin levels adequate hypothalamus less sensitive to estrogen as puberty nears; releases GnRH in rhythmic pulse-like manner  FSH and LH release  ovarian hormone release © 2013 Pearson Education, Inc.

5 Establishing the Ovarian CycleGonadotropin levels increase ~ four years; no ovulation; no pregnancy Then adult cyclic pattern achieved and menarche occurs First menstrual period ~ Three years before cycle regular and all ovulatory © 2013 Pearson Education, Inc.

6 Hormonal Interactions During a 28-Day Ovarian Cycle1. GnRH  release of FSH and LH 2. FSH and LH  growth of several follicles, and hormone release 3. plasma estrogen levels inhibit release of FSH and LH estrogen levels enhance further estrogen output Inhibin from granulosa cells also inhibits FSH release © 2013 Pearson Education, Inc.

7 Hormonal Interactions During a 28-Day Ovarian Cycle4. When estrogen levels high  brief positive feedback on brain and anterior pituitary 5. Stored LH, and some FSH, suddenly released by anterior pituitary at midcycle  surge triggers ovulation  primary oocyte to complete meiosis I  secondary oocyte Secondary oocyte  meiosis II © 2013 Pearson Education, Inc.

8 Hormonal Interactions During a 28-Day Ovarian CycleLH effects at midcycle Increases local vascular permeability Triggers inflammatory response  metalloproteinase release  weakens ovarian wall  Blood flow stops through protruding follicle wall  wall thins, bulges, ruptures  hole (stigma)  Oocyte with corona radiata exits (ovulation) © 2013 Pearson Education, Inc.

9 Hormonal Interactions During a 28-Day Ovarian CycleAfter ovulation Estrogen levels decline LH transforms ruptured follicle  corpus luteum LH stimulates corpus luteum  progesterone and some estrogen almost immediately Progesterone helps maintain stratum functionalis Maintains pregnancy, if occurs © 2013 Pearson Education, Inc.

10 Hormonal Interactions During a 28-Day Ovarian Cycle6. Negative feedback (from rising plasma progesterone and estrogen levels) inhibits LH and FSH release Inhibin, from corpus luteum and granulosa cells, enhances effect Declining LH ends luteal activity, inhibits follicle development © 2013 Pearson Education, Inc.

11 Hormonal Interactions During a 28-Day Ovarian CycleIf no fertilization Corpus luteum degenerates when LH levels fall  sharp decrease in estrogen and progesterone  ends blockage of FSH and LH secretion  Cycle starts anew Oocyte actually activated 12 months prior to ovulation, not 14 days © 2013 Pearson Education, Inc.

12 Figure 27.21 Regulation of the ovarian cycle.Slide 1 Hypothalamus Hypothalamus GnRH Positive feedback exerted by large in estrogen output by maturing follicle. 4 4 GnRH 6 Travels via portal blood 1 Anterior pituitary 1 4 Progesterone Estrogens Inhibin LH surge FSH LH Ruptured follicle 5 2 2 6 Thecal cells Slightly elevated estrogen and rising inhibin levels inhibit FSH secretion. 2 3 Androgens 5 Granulosa cells 2 Mature vesicular follicle Inhibin Convert androgens to estrogens Ovulated secondary oocyte Corpus luteum 2 Estrogens Early and midfollicular phases Late follicular and luteal phases Stimulates Inhibits © 2013 Pearson Education, Inc.

13 Figure 27.21 Regulation of the ovarian cycle.Slide 2 Hypothalamus GnRH Travels via portal blood 1 Anterior pituitary 1 FSH LH Early and midfollicular phases © 2013 Pearson Education, Inc.

14 Figure 27.21 Regulation of the ovarian cycle.Slide 3 Hypothalamus GnRH Travels via portal blood 1 Anterior pituitary 1 FSH LH 2 2 Thecal cells 2 Androgens Granulosa cells 2 Mature vesicular follicle Inhibin Convert androgens to estrogens 2 Estrogens Early and midfollicular phases © 2013 Pearson Education, Inc.

15 Figure 27.21 Regulation of the ovarian cycle.Slide 4 Hypothalamus GnRH Travels via portal blood 1 Anterior pituitary 1 FSH LH 2 2 Thecal cells Slightly elevated estrogen and rising inhibin levels inhibit FSH secretion. 2 3 Androgens Granulosa cells 2 Mature vesicular follicle Inhibin Convert androgens to estrogens 2 Estrogens Early and midfollicular phases © 2013 Pearson Education, Inc.

18 Figure 27.21 Regulation of the ovarian cycle.Slide 7 Hypothalamus Hypothalamus GnRH 4 Positive feedback exerted by large in estrogen output by maturing follicle. 4 GnRH 6 Travels via portal blood 1 Anterior pituitary 1 4 Progesterone Estrogens Inhibin LH surge FSH LH Ruptured follicle 5 2 2 6 Thecal cells Slightly elevated estrogen and rising inhibin levels inhibit FSH secretion. 2 3 Androgens 5 Granulosa cells 2 Mature vesicular follicle Inhibin Convert androgens to estrogens Ovulated secondary oocyte Corpus luteum 2 Estrogens Early and midfollicular phases Late follicular and luteal phases Stimulates Inhibits © 2013 Pearson Education, Inc.

19 Plasma hormone level LH FSHFigure 27.22a Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus. LH Plasma hormone level FSH Fluctuation of gonadotropin levels: Fluctuating levels of pituitary gonadotropins (follicle-stimulating hormone and luteinizing hormone) in the blood regulate the events of the ovarian cycle. © 2013 Pearson Education, Inc.

20 Primary follicle Secondary follicle Vesicular follicle OvulationFigure 27.22b Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus. Primary follicle Secondary follicle Vesicular follicle Ovulation Corpus luteum Degenerating corpus luteum Follicular phase Luteal phase Ovulation (Day 14) Ovarian cycle: Structural changes in the ovarian follicles during the ovarian cycle are correlated with (d) changes in the endometrium of the uterus during the uterine cycle. © 2013 Pearson Education, Inc.

21 The Uterine (Menstrual) CycleCyclic changes in endometrium in response to fluctuating ovarian hormone levels Three phases Days 1–5 - menstrual phase Days 6–14 - proliferative (preovulatory) phase Days 15–28 - secretory (postovulatory) phase (constant 14-day length) © 2013 Pearson Education, Inc.

22 Menstrual phase (Days 1 - 5)Uterine Cycle Menstrual phase (Days 1 - 5) Ovarian hormones at lowest levels Gonadotropins beginning to rise Stratum functionalis shed; menstrual flow (blood and tissue) days By day 5 growing ovarian follicles produce more estrogen © 2013 Pearson Education, Inc.

23 Proliferative phase (Days 6 - 14)Uterine Cycle Proliferative phase (Days ) Rising estrogen levels prompt generation of new stratum functionalis layer; increased synthesis of progesterone receptors in endometrium; glands enlarge and spiral arteries increase in number Normally thick, sticky cervical mucus thins in response to rising estrogen (allows sperm passage) Ovulation occurs at end of proliferative phase © 2013 Pearson Education, Inc.

24 Secretory phase (Days 15 – 28)Uterine Cycle Secretory phase (Days 15 – 28) Most constant timewise Endometrium propares for embryo Rising progesterone levels prompt Functional layer  secretory mucosa Endometrial glands secrete nutrients Formation of cervical mucus plug © 2013 Pearson Education, Inc.

25 If fertilization does not occurUterine Cycle If fertilization does not occur Corpus luteum degenerates toward end of secretory phase Progesterone levels fall Spiral arteries kink and spasm Endometrial cells begin to die; glands regress Spiral arteries constrict again, then relax and open wide Rush of blood fragments weakened capillary beds and functional layer sloughs © 2013 Pearson Education, Inc.

26 Estrogens ProgesteroneFigure 27.22c Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus. Plasma hormone level Estrogens Progesterone Fluctuation of ovarian hormone levels: Fluctuating levels of ovarian hormones (estrogens and progesterone) cause the endometrial changes of the uterine cycle. The high estrogen levels are also responsible for the LH/FSH surge in (a). © 2013 Pearson Education, Inc.

27 Blood vessels Basal layer Days 1 5 10 15 20 25 28Figure 27.22d Correlation of anterior pituitary and ovarian hormones with structural changes of the ovary and uterus. Endometrial glands Blood vessels Menstrual flow Functional layer Basal layer Days 1 5 10 15 20 25 28 Menstrual phase Proliferative phase Secretory phase The three phases of the uterine cycle: • Menstrual: The functional layer of the endometrium is shed. • Proliferative: The functional layer of the endometrium is rebuilt. • Secretory: Begins immediately after ovulation. Enrichment of the blood 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. © 2013 Pearson Education, Inc.

28 Promote oogenesis and follicle growth in ovary 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 © 2013 Pearson Education, Inc.

29 Induce secondary sex characteristicsEffects of Estrogens Induce secondary sex characteristics Growth of breasts Increased deposit of subcutaneous fat (hips and breasts) Widening and lightening of pelvis © 2013 Pearson Education, Inc.

30 Metabolic effects (not true secondary sex characteristics)Effects of Estrogens Metabolic effects (not true secondary sex characteristics) Maintain low total blood cholesterol and high HDL levels Facilitate calcium uptake © 2013 Pearson Education, Inc.

31 Effects of ProgesteroneProgesterone works with estrogen to establish and regulate uterine cycle Promotes changes in cervical mucus Effects of placental progesterone during pregnancy Inhibits uterine motility Helps prepare breasts for lactation © 2013 Pearson Education, Inc.

32 Female Sexual ResponseInitiated by touch and psychological stimuli Clitoris, vaginal mucosa, bulbs of vestibule, and breasts engorge with blood; nipples erect Vestibular gland secretions lubricate vestibule Orgasm accompanied by muscle tension, increase in pulse rate and blood pressure, and rhythmic contractions of uterus © 2013 Pearson Education, Inc.

33 Female Sexual ResponseFemales have no refractory period after orgasm; can experience multiple orgasms in single sexual experience Orgasm not essential for conception Female libido prompted by dehydroepiandrosterone (DHEA) Adrenal cortex hormone © 2013 Pearson Education, Inc.

34 Sexually Transmitted Infections (STIs)Also called sexually transmitted diseases (STDs) or venereal diseases (VDs) U.S. – highest rates of infection among developed countries Latex condoms help prevent spread Single most important cause of reproductive disorders © 2013 Pearson Education, Inc.

35 Commonly called "the clap" Gonorrhea Commonly called "the clap" Bacterial infection of mucosae of reproductive and urinary tracts Spread by contact with genital, anal, and pharyngeal mucosae Number of cases in U.S. declining © 2013 Pearson Education, Inc.

36 Treatment - antibiotics, but resistant strains becoming prevalentGonorrhea Signs and symptoms Males Urethritis, painful urination, discharge of pus Females 20% display no signs or symptoms Abdominal discomfort, vaginal discharge, or abnormal uterine bleeding Can result in pelvic inflammatory disease and sterility Treatment - antibiotics, but resistant strains becoming prevalent © 2013 Pearson Education, Inc.

37 Bacterial infection transmitted sexually or contracted congenitallySyphilis Bacterial infection transmitted sexually or contracted congenitally Infected fetuses stillborn or die shortly after birth Infection asymptomatic for 2–3 weeks Painless chancre appears at site of infection; disappears in few weeks © 2013 Pearson Education, Inc.

38 Treatment - penicillinSyphilis If untreated, secondary signs appear several weeks later for 3–12 weeks, then disappear Pink skin rash, fever, and joint pain Latent period may or may not progress to tertiary syphilis, characterized by gummas (lesions of CNS, blood vessels, bones, and skin) Treatment - penicillin © 2013 Pearson Education, Inc.

39 Chlamydia Most common bacterial STI in United StatesResponsible for 25–50% of all diagnosed cases of pelvic inflammatory disease Symptoms - urethritis; penile and vaginal discharges; abdominal, rectal, or testicular pain; painful intercourse; irregular menses Can cause arthritis and urinary tract infections in men; sterility in women; newborns contract in birth canal  trachoma (painful eye infection), respiratory tract inflammation Treatment - tetracycline © 2013 Pearson Education, Inc.

40 Most common curable STI in active young women in U.S. Trichomoniasis Most common curable STI in active young women in U.S. Parasitic infection; easily, inexpensively treated Yellow-green vaginal discharge with strong odor; some symptomless © 2013 Pearson Education, Inc.

41 Viral Infections Genital warts Caused by human papillomavirus (HPV)Second most common STI in United States Increased risk of cancers in infected body regions Linked to 80% cases of invasive cervical cancer; most strains do not cause cancer Treatment difficult; controversial © 2013 Pearson Education, Inc.

42 Viral Infections Genital herpes Caused by herpes simplex virus 2Characterized by latent periods and flare-ups Congenital herpes can cause malformations of fetus Treatment - acyclovir and other antiviral drugs © 2013 Pearson Education, Inc.

43 Developmental Aspects: Determination of Genetic SexOf 46 chromosomes in fertilized egg, two (one pair) are sex chromosomes Two sex chromosomes – X chromosome (large); Y chromosome (quite small) Females are XX; each ovum always has an X chromosome Males are XY, so ~50% of sperm contain X, ~50% contain Y © 2013 Pearson Education, Inc.

44 Developmental Aspects: Determination of Genetic SexX egg + X sperm  XX (female offspring) X egg + Y sperm  XY (male offspring) The SRY gene on Y chromosome initiates testes development and maleness © 2013 Pearson Education, Inc.

45 Developmental Aspects: Sexual DifferentiationSexually indifferent stage Gonads begin development in fifth week as gonadal ridges Paramesonephric (Müllerian) ducts (future female 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 © 2013 Pearson Education, Inc.

46 Developmental Aspects: Development of External GenitaliaGenital 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 © 2013 Pearson Education, Inc.

48 Glans penis Urethral folds Anus Glans penis Penis Scrotum AnusFigure 27.24b Development of homologous structures of the external genitalia in both sexes. Approximately 5 weeks Glans penis Urethral folds Labioscrotal swellings (scrotum) Anus Glans penis Penis Scrotum Anus Male development © 2013 Pearson Education, Inc.

50 Development Aspects: Descent of the GonadsAbout two months before birth Testosterone stimulates migration of testes toward scrotum Gubernaculum - fibrous cord from each testis to scrotum or from ovary to labium majus; guides descent Ovaries also descend, but stopped by broad ligament at pelvic brim © 2013 Pearson Education, Inc.

52 Development Aspects: PubertyFSH and LH elevated at birth but drop and remain low during prepubertal years Reproductive organs grow to adult size and become functional – puberty Occurs in response to rising levels of gonadal hormones Secondary sex characteristics appear Earliest time that reproduction is possible © 2013 Pearson Education, Inc.

53 Has occurred when menses have ceased for an entire year Menopause Has occurred when menses have ceased for an entire year No equivalent to menopause in males Males continue to produce sperm well into eighth decade of life, though numbers and motility decrease © 2013 Pearson Education, Inc.

54 Declining estrogen levels Menopause Declining estrogen levels  Atrophy of reproductive organs and breasts Irritability and depression in some Hot flashes as skin blood vessels undergo intense vasodilation Gradual thinning of skin and bone loss Increased total blood cholesterol levels and falling HDL © 2013 Pearson Education, Inc.

55 Treatment with estrogen-progesterone preparations given for yearsMenopause Treatment with estrogen-progesterone preparations given for years Women's Health Initiative research reported increased risk of heart disease (51%), invasive breast cancer (24%), stroke (31%), dementia (risk doubled) Smallest does for shortest time alright to reduce symptoms if no breast cancer or mutated BRCA gene © 2013 Pearson Education, Inc.