The Female Reproductive System

1. The Female Reproductive System

3. Functions Fertilization of the egg Capture the egg 1. Produce egg; 2. produce estrogen and progesterone 1.Implantation of fertilized egg; 2.embryo developing 3. Lining changes in menstrual cycle Secret mucus 1.Receive sperm; 2. Discharge of fluid during menstruation; 3. Birth of baby

4. The structure of one ovary and stages the developing egg 卵母细胞 卵泡 输卵管伞 基质

5. 卵原细胞 颗粒细胞

6. The Female Reproductive System – Oogenesis (卵子发生) Puberty 卵泡膜细胞 颗粒细胞

7. The Female Reproductive System – Oogenesis (卵子发生)

8. The Female Reproductive System – Oogenesis (卵子发生) Oogenesis: production of haploid gametes in females; The full sequence of meiosis is not completed until fertilization

9. Ovulation

10. Ovarian Hormones Synthesis: Granulosa cell: E, Lutein cell: P, E • The two-stage model of estrogen synthesis: • androgen precursors are synthesized in the outer layer (theca cells) of the ovarian follicles and • diffuse to the inner layer (granulosa cells) for conversion to estrogens; • LH drives the former, FSH the latter.

11. Hormones of the Ovaries - Estrogen

12. Hormones of the Ovaries - Progesterone Theca cells Granulosa cells

13. Estrogen and Progesterone

15. Estrogens: Estradiol; Estrone; Estriol Progestins: Progesterone Estradiol Sources: Ovary, adrenal cortex, placenta Types: β-Estradiol: from ovary, the major estrogen Estrogenic potency: 12 times that of estrone and 80 times that of estriol Estrone Formed in the peripheral tissues from androgens secreted by the adrenal cortices and by ovarian thecal cells Estriol: weak An oxidative product derived from both estradiol and estrone mainly in the liver Progestins: Progesterone, secreted by the corpus luteum and placenta

16. Estrogen levels with age

17. Chemistry of Ovarian Hormones Transport in the blood binding with albumin Specific estrogen- and progesterone-binding globulins Rapidly released to the tissues - about 30 mins Fate of estrogens: Liver: estradiol and estrone → estriol Liver function↓ → ↑ estrogen activity Fate of progesterone Liver: P → pregnanediol (孕二醇) - estimate the rate of P formation from the rate of pregnanediol excretion in the urine

18. Functions of estrogens

19. Functions of Progesterone

20. Menstrual Cycle Monthly rhythmical changes in the rates of secretion of the female hormones and corresponding physical changes in the ovaries and other sexual organs (e. g. the uterus) Ovarian cycle:Only a single ovum is normally released Endometrium cycle Length: average about 28 days Start at puberty - Menarche: 11 ~15 years of age Stop at menopause 40 ~ 50 years of age

21. Ovarian Cycle Follicular phase: FSH - Day 1 to day 14 Luteal phase: LH - Day 14 to day 28

22. Follicular phase: Primordial follicle, Primary follicle, Antral follicle, and mature follicle Primordial follicle （始基卵泡、原始卵泡）: ovum + a single layer of granulosa cells During childhood - Oocyte maturation-inhibiting factor Primary follicles （初级卵泡）: After puberty, FSH causes accelerated growth of 6 to 12 primary follicles each month; granulosa cells + theca interna （内膜层） + theca externa Antral follicles （有腔卵泡） Follicular fluid (E) Vesicular follicles E→granulosa cells → FSH-Rs↑ E+ FSH → granulosa cells → LH-Rs↑ E+ LH → proliferation and secretion of follicular thecal cells

23. Mature follicle Before ovulation Only one each month D= 1 to 1.5 cm at the time of ovulation Atresia（闭锁、萎缩） of the remainder Ovulation - 14 days after the onset of menstruation Ovulatory Surge of LH, rising 6- to 10-fold, peak at about 16 hrs before ovulation Ovum + corona radiata （放射冠）

24. Luteal phase • Luteinization • - the remaining granulosa and theca interna cells →luteal cells • Depending on LH • Corpus luteum • Pand E (granulosa cells) • Androgens (theca interna cells) • Corpus albicans （白体） • 12 days after ovulation • Losing secretory function

25. Involution （退化） of the corpus luteum and onset of the next ovarian cycle Involution E and P→ strong feedback effects → FSH and LH↓ →involution Inhibin (luteal cells) →FSH ↓ →involution Onset of the next ovarian cycle 2 days before menstruation begins Sudden cessation of secretion of E, P and inhibin → removal of the feedback inhibition → FSH and LH ↑ → initiate growth of new follicles

26. Summary After every 28 days, gonadotropic hormones cause about 8 to 12 new follicles to begin to grow in the ovaries. One of these follicles finally becomes ‘mature’ and ovulates on the 14th day of the cycle. During the growing of the follicles, estrogen is mainly secreted. After ovulation, the secretory cells of the ovulating follicle develop into a corpus luteum that secretes large amount of P and E. After another 2 weeks, the corpus luteum degenerates, whereupon P and E decrease greatly and menstruation begins.

27. Menstrual Cycle • Endometrial（子宫内膜） cycle - Phases • - Proliferative phase (estrogen phase) : 5 -14 days • Secretory phase (Progestational phase): 15 - 28 days • - Menstruation: 1 – 5 days

28. Endometrial cycle – Proliferative phase: Before ovulation, under the influence of Es, stromal cells and epithelial cells proliferate New blood vessels grow Endometrium increases in thickness (3 - 5mm at the time of ovulation) Endometrial glands secret stringy mucus along the length of the cervical canal for help guide sperm Endometrial cycle - Secretory phase: After ovulation, under the influence of Es and P Es cause additional cellular proliferation while P causes swelling and secretory development of the endometrium（子宫内膜） Glands increase in tortuosity（弯曲度） Increased deposits of lipid and glycogen in stromal cells Blood vessels become highly tortuosity Endometrium increases in thickness – 5 - 6mm at the peak of this phase, with purpose of producing a highly secretory endometrium that contains large amounts of stored nutrients to provide appropriate conditions for implantation of a fertilized ovum

29. Endometrial cycle - Menstruation: 4 -7 days Caused by the reduction of Es and P Involution of the endometrium to 65% Vasospasm + ↓ nutrients + loss of hormonal stimulation → necrosis and hemorrhage→ all the superficial layers desquamate → uterine contraction Menstrual fluid： Necrotic material + blood + tremendous numbers of leukocytes 40ml blood and 35ml serous fluid are lost Nonclotting - release of fibrinolysin (纤溶酶) Highly resistant to infection

30. Menses, days 0 to 7: Levels of LH, FSH, estrogen, and progesterone are low. The lining of the uterus cannot be maintained, and the uterine lining is lost.

31. The proliferative phase, days 7 to 14: The follicle increases production of estrogen, causing LH to surge. The follicle ruptures, and the egg is expelled. Estrogen and progesterone stimulate growth of the uterine lining.

32. The secretory/luteal phase, days 14 to 28: The follicle develops into corpus luteum and increases production of progesterone that prepares the uterus for implantation. If fertilization and implantation do not occur, the corpus luteum degenerates into scar tissue called the corpus albicans and progesterone levels drop.

34. Positive feedback effect of E Before ovulation ↑ E → LH ↑ ↑ Preovulatory LH surge 24-48 hrs before ovulation For 1-2 days Negative feedback effects of E, P and inhibin E in small amounts or E+P → anterior pituitary gland or hypothalamus (lesser) → LH and FSH↓ Inhibin → anterior pituitary gland → FSH and LH (lesser)↓

36. Regulation of menstrual cycle Hypothalamic-pituitary-ovarian system Hypothalamus GnRH: ↑FSH and LH Pituitary FSH: ↑ Follicular growth, E,P secretion LH: ovulation, corpus luteum formation, P secretion Ovary E: negative and positive feedback effects P: negative feedback effect

37. Release of GnRH Hypothalamic center Mediobasal hypothalamus (arcuate nuclei) Psychic factors→ limbic system → arcuate nuclei → to modify the intensity and frequency of GnRH release → to modify female sexual function Pulsatile secretion - in pulses lasting 5-25 mins which occur every 1-2 hrs - essential to its function - causes intermittent output of LH secretion about 90 mins →Pulsatile release of LH

38. Regulation of menstrual cycle (正负反馈调节机制)

40. Menstrual Cycle: hormones Small increases in the secretion of gonadotropins (LH & FSH) lead to follicular maturation, including an increase in the synthesis and secretion of ovarian steroid hormones (1-7). Ovulation is provoked by a surge in LH and marks the transition to the luteal phase of the cycle, characterized by high levels of progesterone (8-14). Eventually, (15) a decrease in LH leads to luteolysis, and the withdrawal of steroid support for a thick, active uterus.

41. Anovulatory cycles The preovulatory surge of LH is not of sufficient magnitude No ovulation Failure of development of the corpus luteum Almost no secretion of P Cyclical variations of the sexual cycle continue Cycle is shortened by several days Rhythm continues The first few cycles after the onset of puberty Several months to years before menopause（绝经）

42. Menopause 40 ~ 50 years Sexual cycle: irregular →cease The remaining primordial follicles become atretic（闭锁） Female sex hormones↓ FSH and LH are produced in large and continuous quantities Physiological changes in the function of the body because of loss of Es: Hot flushes（潮热） Psychic sensation of dyspnea Irritability Fatigue Anxiety Strength and calcification of bones ↓ To avoid severe symptoms - Daily administration of an E in small quantities and gradually decrease the dose

43. Female fertility Fertile period of each sexual cycle Intercourse must occur sometime between 4 and 5 days before ovulation up to a few hours after ovulation in order to fertilize Ovum remains viable and capable of being fertilized after it is expelled no longer than 24 hrs A few sperm can remain fertile in the female reproductive tract for up to five days

44. Female sterility • About 1/6 ~ 1/8 marriages is infertile - ~ 60% of which: female sterility • The most common causes • 1) Anovulation: Hyposecretion of gonadotropic hormones (treated by hCG); • Abnormal ovaries; Thick ovarian capsules • Methods to determine whether ovulation occurs: to chart a woman’s body temperature throughout the cycle; T rises abruptly at the time of ovulation • 2) Endometriosis（子宫内膜异位） :Endometrial tissue grows and even menstruates in the pelvic cavity surrounding the uterus, fallopian tubes and ovaries, causing fibrosis throughout the pelvis and occluding the fallopian tubes • 3) Other causes • Salpingitis（输卵管炎） :Inflammation of the fallopian tubes → occluding; • Secretion of abnormal mucus by the uterine cervix: E → mucus secretion ↑ → mucous ‘threads’ • Viscous mucus plug (low-grade infection or inflammation, or abnormal hormonal stimulation of the cervix)

45. Pregnancy 桑葚胚 囊胚

46. Fertilization of the ovum Implantation of the blastocyst（胚泡）

47. The morula is differentiated into two groups of cells: a small group of internal blastomeres（分裂球）called the inner cell mass or embryoblast（成胚细胞）which gives rise to the embryo; the surrounding cells, termed the outer cell mass or trophoblast（滋养层）, which give rise to the placenta and membranes.

48. 绒毛膜 After the end of the first trimester, the placenta is more fully developed, including its nutritive/exchange relationship between the maternal and fetal circulations, and its steroid products provide hormonal support for the uterus.

49. Placental hormones: Human chorionic gonadotropin (hCG，人绒毛膜促性腺激素) ; Human chorionic somatomammotropin (hCS，人绒毛膜生长催乳素) Metabolites of hCG in the urine are an ‘early indicator’ of pregnancy. The critical transition from uterine-ovarian to placental steroids occurs at the end of the first trimester, a period with the largest risk of miscarriage.