Chapter 20

1. Chapter 20 Reproduction

2. Objectives • Describe hormonal changes that occur during puberty, the mechanisms that may control the onset of puberty, and the secondary sex characteristics that develop during puberty. • Explain how the secretions of FSH and LH are regulated in the male and describe the actions of these hormones on the testes. • Describe the stages of spermatogenesis and describe the effects of androgens on the male accessory sex organs. • Describe oogenesis and the stages of follicle development through ovulation and formation of the corpus luteum.

3. Objectives (continued) • Explain the hormonal interactions involved in the control of ovulation. • Describe the changes in the secretion of ovarian sex steriods during a nonfertile cycle and explain the functions and fate of the corpus luteum. • Explain how the secretion of FSH and LH is controlled through negative and positive feedback mechanisms during a menstrual cycle.

4. Objectives (continued) • Describe the cyclic changes that occur in the endometrium and the hormonal mechanisms that cause these changes. • Describe the acrosomal reaction and the events that occur at fertilization, blastocyst formation and implantation. • List the hormones secreted by the placenta and describe their actions. • Discuss factors that stimulate uterine contractions during labor and parturition, and explain now the onset of labor may be regulated.

5. Sexual Determination • Each zygote inherits 23 chromosomes from the mother and 23 chromosomes from the father. • Produce 23 pairs of homologous chromosomes. • First 22 pairs of chromosomes are autosomal chromosomes. • 23rd pair are sex chromosomes. • Diploid cell undergoes meiotic division, its daughter cells receive only 1 chromosome from each homologous pair. • The gametes are haploid. • Chromosomal gender of zygote determined by fertilizing sperm.

6. Formation of Testes • First 40 days after conception the gonads of males and females are similar in appearance. • Cells that will give rise to spermatogonia and oogonia migrate from yolk sac to developing embryonic gonads. • Testis-determining factor (TDF) promotes the conversion to testes: • Seminiferous tubules appear within 43-50 days following conception. • Produce: • Germinal cells: sperm. • Nongerminal cells: Sertoli cells. • Leydig cells: • Appear about day 65.

7. Formation of Testes (continued) • Leydig cells secrete testosterone. • Begins at the 8th week and peaks at 12-14th week. • Masculinizes embryonic structures. • [Testosterone] then declines to very low levels until puberty. • Testes descend into scrotum shortly before birth.

8. Formation of Ovaries • Absence of Y chromosome and TDF, female develop ovaries. • Ovarian follicles do not appear until 2nd trimester, about day 105.

9. Chromosomal Sex and Development of Embryonic Gonads Insert fig. 20.4

10. Development of Accessory Sex Organs and Genitalia • Presence or absence of testes determines the accessory sex organs and external genitalia. • Male accessory organs derived from wolffian ducts. • Sertoli cells secrete MIF (müllerian inhibition factor). • Female accessory organs derived from mullerian ducts. Insert fig. 20.5

11. Disorders of Embryonic Sexual Development • Hermaphroditism: • Both ovarian and testicular tissue is present in the body. • Pseudohermaphrodite: • Individual with either testes or ovaries but not both. • Have accessory sex organs and external genitalia that are incompletely developed or inappropriate. • Most common cause of female pseudohemaphroditism is congenital adrenal hyperplasia. • In the male, one cause is testicular feminizing syndrome: • Normal functioning testes, but lack receptors for testosterone.

12. Endocrine Regulation of Reproduction • Hypothalamus releases LHRH (GnRH) into hypothalamo-hypophyseal portal vessels. • Anterior pituitary secretes: • LH (luteinizing hormone). • FSH (follicle-stimulating hormone). • Secreted in pulsatile fashion to prevent desensitization and down regulation of receptors.

13. Endocrine Interactions • Anterior pituitary secretes LH and FSH. • Secretion of LH and FSH stimulated by LHRH (GNRH). • Primary effects of LH and FSH on gonads: • Stimulation of spermatogenesis and oogenesis. • Stimulation of gonadal hormone secretion. • Maintenance of gonadal structure.

14. Endocrine Regulation • Negative feedback: • Inhibits GnRH from hypothalamus. • Inhibits anterior pituitary response to GnRH. • Inhibin secretion inhibits anterior pituitary release of FSH. • Female: • Estrogen and progesterone. • Male: • Testosterone. Insert fig. 20.9

15. Onset of Puberty • FSH and LH secretion is high in newborn, but falls to low levels in few weeks. • At puberty: • Brain maturation increases GnRH secretion. • Decreased sensitivity of gonadotropin to negative feedback. • During late puberty, pulsatile secretion of LH and FSH increase during sleep. • Stimulate a rise in sex steroid secretion.

16. Onset of Puberty (continued) • Stimulates rise in testosterone and estradiol-17b. • Produce secondary sexual characteristics. • Age of onset related to the % of body fat and physical activity in the female • Leptin secretion from adipocytes may be required for puberty. Insert fig. 20.10

17. Pineal Gland • Secretes melatonin. • Stimulated by postganglionic sympathetic neurons. • Activity of these neurons is inhibited by nerve tracts that are activated by light. • Secretion influenced by light-dark cycles. • Inhibits gonadotropin secretion. • Role in humans not established.

18. 4 Phases of Human Sexual Response Excitation phase: • Myotonia and vasocongestion. • Engorgement of a sexual organ with blood. • Erection of the nipples in both genders. • Plateau phase: • Clitoris becomes partially hidden. • Erected nipples become partially hidden by swelling of areolae. • Orgasm: • Uterus and orgasmic platform of vagina contract. • Contractions accompanying ejaculation. • Resolution phase: • Body returns to preexcitation conditions. • Men enter refractory period.

19. Male Reproductive System • Testes: • Seminiferous tubules: • Contain receptor proteins for FSH in Sertoli cells. • FSH stimulates spermatogenesis to occur. • Leydig cells: • LH stimulates secretion of testosterone. • Contain receptor proteins for LH. Insert fig. 20.12

20. Control of LH and FSH Secretion • Negative feedback: • Testosterone inhibits LH and GnRH production. • Maintain relatively constant secretion of LH and FSH. • Declines gradually in men over 50 years of age. • Testosterone converted to DHT, which inhibits LH. • Inhibin inhibits FSH secretion. • Aromatization reaction producing estradiol in the brain, is required for the negative feedback effects. Insert fig. 20.13

21. Derivatives of Testosterone Insert fig. 20.14

22. Endocrine Function of the Testes • Testosterone and its derivatives are responsible for initiation and maintenance of body changes in puberty. • Stimulate growth of muscles, larynx, and bone growth until sealing of the epiphyseal discs. • Promote hemoglobin synthesis. • Act in paracrine fashion, responsible for spermatogenesis. Insert fig. 20.15

23. Estrogen Secretion • Sertoli and Leydig cells secrete small amounts of estradiol. • Receptors found in Sertoli and Leydig cells and accessory organs. • May be responsible for: • Negative feedback in brain. • Sealing of epiphyseal plates. • Regulatory function in fertility.

24. Spermatogenesis • Spermatogonia: • Replicate initially by mitosis. • One of the 2 primary spermatocytes undergoes meiosis: • 2 nuclear divisions: • 1st meiotic division produces 2 secondary spermatocytes. • 2nd meiotic division produces 4 spermatids. Insert 20.16

25. Spermiogenesis • Maturation of spermatozoa. • Phagocytosis of cytoplasm by the Sertoli cells. • Cytoplasm is eliminated. Insert fig. 20.18

26. Sertoli Cells • Form blood-testes barrier: • Prevents autoimmune destruction of sperm. • Produce FAS ligand which binds to the FAS receptor on surface to T lymphocytes, triggering apoptosis of T lymphocytes. • Prevents immune attack. • Secrete inhibin. • Phagocytize residual bodies: • May transmit information molecules from germ cells to Sertoli cells. • Secrete androgen-binding protein (ABP): • Binds to testosterone and concentrates testosterone in the tubules.

27. Hormonal Control of Spermatogenesis • Formation of primary spermatocytes and entry into early prophase I, begin during embryonic development. • Spermatogenesis arrested until puberty. • Testosterone required for completion of meiosis and spermatid maturation. • Secrete paracrine regulators: • IGF-1. • Inhibin. • Transforming growth factor. • FSH necessary in the later stages of spermatid maturation.

28. Male Accessory Organs • Epididymis responsible for: • Maturational changes. • Resistance to pH changes and temperature. • Storage of sperm between ejaculations. • Ductus (vas) deferens: • Carries sperm from epididymis into pelvic cavity. • Seminal vesicles secrete: • Fructose. • Prostate secretes: • Alkaline fluid. • Citric acid. • Ca2+. • Coagulation proteins.

29. Erection, Emission, and Ejaculation • Erection: • Controlled by hypothalamus and spinal cord. • Increased vasodilation of arterioles. • Parasympathetic nervous system. • NO is the NT. • Blood flow into the erectile tissues of the penis. • Emission: • Movement of semen into the urethra. • Stimulated by sympathetic nervous system. • Ejaculation: • Forcible expulsion of semen from the urethra out of the penis. • Stimulated by sympathetic nervous system.

30. Male Fertility • 60-150 million sperm/ml ejaculate. • Oligospermia: • Sperm count of < 20 million/ml ejaculate. • Decreased fertility caused by heat, pharmaceuticals, and illicit drugs. • Male contraception: • Compounds that suppress gonadotropin secretion. • Testosterone. • Progesterone and GnRH antagonist. • Vasectomy: • Each ductus deferens is cut and tied. • Interferes with sperm transport. • May develop anti-sperm antibodies.

31. Female Reproductive System • Ovaries: • Contain a large number of follicles which enclose ova. • Extensions called fimbriae partially cover each ovary. • At ovulation, secondary oocyte is extruded. • Fallopian (uterine) tubes: • Ova drawn into the tubes by cilia.

32. Female Reproductive System (continued) • Uterus: • Has 3 layers: • Perimetrium: • Outer layer of connective tissue. • Myometrium: • Smooth muscle layer. • Endometrium: • Inner layer of stratified, squamous, nonkeratinized epithelium. • Shed during menstruation. • Vagina: • Cervical mucus plug.

33. Ovarian Cycle • 5 mo. gestation, ovaries contain 6-7 million oogonia. • Oogenesis arrested in prophase of 1st meiotic division (primary oocyte). • Apoptosis occurs: • 2 million primary oocytes at birth. • 400,000 primary oocytes at puberty. • 400 oocytes ovulated during the reproductive years. Insert fig. 20.30

34. Ovarian Cycle (continued) Insert fig. 20.32 • Primary oocytes are contained in primary follicles. • FSH stimulates granulosa cell growth. • Develop into secondary follicles. • Fusion of its vesicles to form the antrum. • Mature graafian follicle. • 1st meiotic division completed (secondary oocyte). • Polar body fragments.

35. Ovarian Cycle (continued) • Secondary oocyte confined to graafian follicle. • Arrested at metaphase II. • Under FSH stimulation: • Theca cells secrete testosterone. • Granulosa cells contain the enzyme aromatase to convert testosterone into estrogen. • Granulosa cells form a ring (corona radiata) around oocyte and form mound (cumullus oophorus). • Between oocyte and corona radiata is zona pellucida. • Provides barrier to the sperm to fertilize the egg.

36. Ovulation • One graafian follicle forms bulge on surface of ovary. • Extrudes secondary oocyte into the uterine tube. • LH causes the empty follicle to become corpus luteum which secretes: • Progesterone and estrogen. • If not fertilized, becomes corpus albicans. Insert fig. 20.33

37. Pituitary-Ovarian Axis • Hormonal interactions between the anterior pituitary and the ovaries. • Anterior pituitary secretes FSH and LH. • Controlled by GnRH. • FSH secretion is slightly greater than LH during early phase of menstrual cycle. • LH secretion greatly exceeds FSH secretion just prior to ovulation. • - feedback.

38. Menstrual Cycle • Menstruation: • Day 1-4/5. • Day 1 is the first day of menstruation. • Duration approximately 28 days. • Secretions of estrogen and progesterone are at their lowest. • Ovaries contain only primary follicles.

39. Follicular Phase • Lasts from day 1 to about 13. • FSH: • Follicles become increasingly sensitive to FSH. • FSH stimulates the production of FSH receptors on the granulosa cells. • Toward the end of the phase, sensitivity of FSH receptors increases. • FSH and estradiol stimulate production of LH receptors in graafian follicle. • Rapid rise in estradiol from granulosa cells. • Negative feedback on LH and FSH.

40. Follicular Phase (continued) • Hypothalamus increases frequency of GnRH pulses. • Augments the ability of anterior pituitary to respond to GnRH, to increase LH secretion. • Positive feedback: • LH surge begins 24 hours before ovulation. • Triggers ovulation. • FSH increase stimulates development of new follicles.

41. Endocrine Control of the Ovarian Cycle

42. Ovulation • Wall of graafian follicle ruptures. • Day 14. • 1st meiotic division is completed.

43. Luteal Phase • LH stimulates formation of the empty follicle into corpus luteum. • Corpus luteum secretes: • Progesterone: • Plasma concentration rapidly rises. • Exerts negative feedback on LH and FSH. • Inhibin: • Suppresses FSH secretion. • Inhibin production decreases towards end of luteal phase.

44. Luteal Phase (continued) • Corpus luteum regresses unless fertilization occurs: • Estradiol decreases. • Progesterone decreases. • Withdrawal of estradiol and progesterone cause menstruation to occur.

45. Cycle of Ovulation and Menstruation Insert fig. 20.35

46. Cyclic Changes in the Endometrium • Proliferative Phase: • Ovary is in follicular phase. • Estradiol stimulates growth of endometrium of stratum functionale. • Spiral arteries develop. • Estradiol: • Stimulate production of receptor proteins for progesterone.

47. Cyclic Changes in the Endometrium (continued) • Secretory phase: • Ovary is in luteal phase. • Progesterone stimulates development of uterine glands, which become engorged with glycogen. • Endometrium becomes thick, vascular, and spongy. • Cervical mucus thickens and becomes sticky.

48. Cyclic Changes in the Endometrium (continued) • Menstrual phase: • Progesterone withdrawl causes constriction of spiral arteries. • Necrosis and sloughing of endometrium occurs. • Lasts 1-5 days.

49. Contraceptive Methods • Contraceptive pill: • Synthetic estrogen combined with synthetic progesterone pills are taken once each day for 3 weeks after the last day of menstruation. • Negative feedback inhibits ovulation. • Placebo pill taken the 4th week permits menstruation. • Rhythm method: • Women measure oral basal body temperature upon awakening daily. • On day of LH surge, there is a slight drop in basal body temperature.

50. Menopause • Cessation of ovarian activity and menstruation. • Age ~ 50 years. • Ovaries are depleted of follicles. • Estradiol and inhibin withdrawl causes hot flashes, and atrophy of the vaginal wall. • LH and FSH increase.