Ai-Min Bao, M.D. Ph.D. Zhejiang University School of Medicine

1. Ai-Min Bao, M.D. Ph.D. Zhejiang University School of Medicine

2. Human Reproductive System Reproduction is the biological processby which new individual organisms are produced Types: Sexualreproduction, Asexual reproduction Human reproduction belongs to sexual reproduction 配子 接合子

3. Fetal Development of the Reproductive System

5. 附睾 输精管 MIH：Müllerian-inhibiting hormone 精囊 尿道 r 输卵管 子宫、宫颈、阴道

6. male female SRY: Sex-determining Region on the Y Chromosome

7. Function: 1. Produce estrogen and progesterone; 2. Produce eggs; 3. Receive the sperm; 4. Provide the optimal conditions for the development of the fetus Function: 1. Produce testosterone; 2. Produce sperm; 3. Deliver sperm to the female vagina.

8. Male reproductive system Primary sexual organ – Gonad (Testis) Accessory sexual organ 尿道球腺

9. Testis： 2 compartments - Seminiferous tubules - Interstitium Ductus deferens （曲）细精管 Epididymis

10. （睾丸间质细胞） Lumen of Seminiferous Tubule Sperm Testis

11. 精细胞 S 初级精母细胞 支持细胞、足细胞 精原细胞

12. Testis Germinal epithelium （睾丸生殖上皮）of the testicle 1: basal lamina; 2: spermatogonia （精原细胞）3: spermatocyte 1st order; 4: spermatocyte 2nd order; 5: spermatid; 6: mature spermatid; 7: Sertoli cell; 8: tight junction (blood testis barrier) 支持细胞 产生 inhibin（抑制素）、ABP （雄激素结合蛋白） 莱氏细胞 产生雄激素

13. Sertoli cell: Glycoprotein, Inhibin A (α β1), Inhibin B (α β2) Function: (-) FSH secretion

14. Spermatogenesis: In all the seminiferous tubules during active sexual life, Stimulated by gonadotropic hormones, Begin at an average age of 13 yr, Decreasing markedly in old age, The entire period: 64 days 有丝分裂 第一次减数分裂 第二次减数分裂

15. Spermatogenesis is the testicular process in adult males that generates haploid gametes (单倍体配子) capable of fertilizing ova. The overall result is that the set of 23 pairs of homologous chromosomes （同源染色体）is reduced to a set of 23 chromosomes per sperm – the corresponding 23 pairs are present in ova.

16. Head: Acrosome, containing enzymes Tail (flagellum): to and fro movement, 1-4 mm/min in a fluid medium Lifetime: Many weeks in the male genital ducts; 24-48 hrs in the ejaculated semen（精液）; Several weeks at lowered temperature; Years below - 100°C; Count: Ejaculated semen during each coitus: 3.5 ml; An average of about 120 million sperm/ml semen (35 ~200 million/ml); < 20 million/ml→ infertile;

17. Infertile: Abnormal physically; Nonmotile or relatively nonmotile

18. Control of Testicular Function Factors that affect spermatogenesis Hormonal factors that stimulate spermatogenesis – Testosterone, LH, FSH Temperature↑ → (-) spermatogenesis Scrotum（阴囊）As a cooling mechanism - Maintain 2°C difference Cryptorchidism （隐睾症） FSH, LH Testis

19. In response to FSH and testosterone, the Sertoli cells support spermatogenesis. They produce inhibin, estrogen In response to LH, the Leydig cells produce steroids, including testosterone.

20. Androgens Steroid hormones (Leydig cells) Types: Testosterone (T, more abundant), Dihydrotestosterone (DHT, more active), Dehydroisoandrosterone (DHIA), Androstenedione（雄烯二酮） Source: Testes Adrenal glands Synthesis: from cholesterol P450scc (side chain cleavage) Secretion Pattern: Pulsatile - Circadian rhythm

21. Androgens At different ages: Stimulated by hCG during fetal development and for 10 or more weeks after birth Stimulated by LH at the onset of puberty Transportation: 30 mins~several hrs+ Albumin+ Gonadal steroid-binding globulin (GBG) Metabolism→ DHT (tissue) or Estrodiol Degradation into inactive products in the liver Excretion from the kidney or gut

22. 孕烯醇酮 雄烯二醇 雄烯二酮

23. Functions of testosterone initiate and maintain spermatogenesis stimulate the descent of testes - usually into the scrotum during the last 2 to 3 months of gestation. If not, administration of T or gonadotropic hormones induce differentiation of male accessory reproductive organs and maintain their function induce male secondary sexual characteristics

24. Functions of testosterone affect the distribution of body hair: ↑ growth of hair over the pubis, face and chest ↓ growth of hair on the top of the head affect the voice - causing hypertrophy of the laryngeal mucosa and enlargement of the larynx→ relatively discordant ‘cracking’ voice → typical adult masculine bass voice induce the development of acne:↑thickness of the skin,↑secretion by the sebaceous glands（皮脂腺）

25. Functions of testosterone inducemuscle development: ↑muscle mass - Synthetic androgens used by athletes Used in old age as a ‘youth hormone’ Effect on bone growth and calcium retention ↑ size and strength of bones ↑ total quantity of bone matrix Causes calcium retention used in older men to treat osteoporosis Stimulate cessation of bone growth Specific effect on the pelvis: A funnel-like shape Effect on metabolism: stimulate protein anabolism ↑ red blood cells Required for sex drive and may enhance aggressive behavior

26. Working mechanism

27. Capacitation of spermatozoa（精子获能） occurs in the female genital tract stimulated by secretions in the vagina, uterus, and uterine tubes results in capacity to pass through the corona radiata involves removal of surface coatings and changes in plasma membrane can be produced in vitro by washing with salt solution

28. Acrosome reaction（顶体反应） stimulated by sperm-binding glycoprotein molecules in the zona pellucida （透明带） accompanied by Ca2+ influx into sperm results in the release of acrosomal enzymes (hyaluronidase, 透明质酸酶）and proteolytic enzymes) involves fusionof the acrosome membrane and plasma Membrane necessary for sperm penetration through the zona pellucida

29. Fertilization（受精） • Process: The cell membranes of the sperm head and of the oocyte fuse with each other to form a single cell • The genetic material of the sperm and the oocyte combine to form a completely new cell genome, containing equal numbers of chromosomes and genes from mother and father • Two important genetic consequences: • The diploid chromosome number is restored (2n) • The genetic sex of the zygote is determined (XX or XY) - the spermatozoa determine the sex of the embryo • There are X - bearing spermatozoa and Y-bearing spermatozoa. The oocyte always contributes an X chromosome

30. Why does only one sperm enter the oocyte? Not entirely known Ca2+ diffuse inward through the oocyte membrane → multiple cortical granules released from the oocyte →substances from the granules permeate all portions of the zona pellucida →prevent binding of additional sperm

31. Regulation of testis function Hypothlamus-pituitary-testis axis Hypothlamus: GnRH (also called LHRH), a 10-amino acid peptide, pulsatile release, secreted intermittently a few minutes at a time once every 1 to 3 hrs, ↑ LH (mainly) and FSH sectretion Pituitary: FSH, LH; glycoproteins, pulsatile release, FSH(+) spermatogenesis, LH↑ T sectretion Negative feedback control of T secretion: ↑T secretion → GnRH secretion↓ → LH secretion↓ →↓ T secretion back to the desired operating level Testis: T: (-) LH secretion, Inhibin: (-) FSH secretion

32. Regulation of testis function Negative feedback control of seminiferous tubule activity: Inhibin ↑ → FSH secretion ↓ → control of spermatogenesis Regulation of spermatogenesis by FSH and T Initiate spermatogenesis FSH+ FSH receptor on the Sertoli cells → Sertoli cells grow and secrete various spermatogenic substances T (DHT) Strong tropic effect on spermatogenesis

33. Point of view Q: ‘At puberty, the levels of GnRH begin to increase (both in boys and girls), the cause of which remains UNCLEAR…’? ------The most important new development is the ‘Kisspeptin’ idea. Kiss1 and GPR54 expression increase dramatically during puberty and most probably trigger the events. Dungan et al., 2006; Endocrinology

34. The Male Reproductive System - Quick Review