1. Animal Science 434 Reproductive Physiology Lec 5: Embryogenesis of the Pituitary and Sexual Development

2. Development of the Pituitary Gland Stomodeum Rathke’s Pouch Infundibulum Brain

7. Migration begins by the 4 week of gestation in cow and human. Germ Cell Migration

8. Migration from endoderm through mesoderm.

9. In birds the migration is via the blood stream.

10. Fetal Kidneys Pronephros –regresses Mesonephros –portions of reproductive tract Metenephros –Adult kindney and urinary ducts

11. Development of Mesenephros and Metenephros

12. Jost Experiments Mesonephric Ducts (Wolffian Ducts) Mesonephric Ducts (Wolffian Ducts) Paramesonephric Ducts (Mullerian Ducts) Paramesonephric Ducts (Mullerian Ducts)

13. Jost Experiments Mesonephric Ducts (Wolffian Ducts) Mesonephric Ducts (Wolffian Ducts) Paramesonephric Ducts (Mullerian Ducts) Testis Epidi dymi s Vas Deferens Seminal Vesicles Ovary Oviduct Uterus

14. Sex Determination: The Jost Paradigm Chromosomal Sex Gonadal Sex Phenotypic Sex Chromosomal Sex Gonadal Sex Phenotypic Sex Hormonal Sex Brain and/or Behavioral Sex

15. Chromosomal Sex Single Pair of sex chromosomes –mammals, some but not all vertebrates Sex is environmentally determined –sea worms, fish, reptiles Multiple sex chromosomes –invertebrates, insects, reptiles Haplodiploidy –bees, spiders Single Pair of sex chromosomes –mammals, some but not all vertebrates Sex is environmentally determined –sea worms, fish, reptiles Multiple sex chromosomes –invertebrates, insects, reptiles Haplodiploidy –bees, spiders

16. Chromosomal Sex A. Drosophila Sex depends on the number of X chromosomes –X or XY or XO  Male –XX or XXX or XXY  Female B. Human (mammals) XY or XXY or XXYY or XXXY or XXXXY  Male (testis) XX or XXX  Female (ovary) XO  Female with incomplete ovarian development XXY or XXYY or XXXY or XXXXY  testis but impaired sperm production C. Conclusion The primary gene that controls testicular differentiation is on the Y chromosome in mammals.

17. The Y Chromosome A. Region coding for testicular development –H-Y Antigen «no longer believed to be involved –SRY «Codes for a DNA binding protein «acts as a transcription factor or assists other transcription factors «the gene products which are transcribed regulate primary sex chord differentiation (formation of seminiferous tubules), androgen production and Anti- Mullerian Hormone (AMH) production «in the absence of the SRY protein, primary sex chord regress and secondary sex chords (egg nests) develop Short arm of Y chromosome

18. The Y Chromosome Cont. B. Other genes on the Y chromosome –Spermatogenesis –androgen production –long bone growth

19. SRY and Birds Birds » females ZW, males ZZ » W chromosome determines sex » SRY is found on the Z chromosome ! SRY is not the only sex determining gene in animals

20. Gonadal Sex

21. Testis Determining Factor (SRY gene product) XY Male Testes develop

22. Rete Tubules Undifferentiated Sex Chords Mullerian Duct Mesonephric Duct (Wolffian Duct) Tunica Albuginea Mesonephric Tubules Testicular Development

23. Rete Tubules Primary, Epithelial or Medullary Sex Chords Primordial germ cells Sertoli Cells Mullerian Duct Wolffian Duct Tunica Albuginea Mesonephric Tubules

24. Hormonal Sex

25. Testis Determining Factor (SRY gene product) Testes develop XY Male Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Testosterone Development of male duct system

26. Testis T T Nucleus TR Wolffian Duct Cells

27. Rete Tubules Seminiferous Tubules Vas Deferens Tunica Albuginea Efferent Ducts (Vas Efferentia) Epididymis

28. Testis Determining Factor (SRY gene product) Testes develop XY Male Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Testosterone Development of male duct system Degeneration of Mullerian duct

29. Vas efferentia

30. Female Development XX Female No TDF Ovaries Develop No AMH Mullerian ducts become the oviducts, uterus, cervix and part of the vagina Testes Determining Factor No Testosterone Wolffian Ducts Regress

31. Mullerian Duct Epithelial Sex Chords Wolffian Duct Regressing Tubules Future Ovarian Cortex Ovarian Development

32. Mullerian Duct Regressing Epithelial Sex Chords Regressing Wolffian Duct Regressing Tubules Future Ovarian Cortex

33. Mullerian Duct Regressing Epithelial Sex Chords Regressing Wolffian Duct Regressing Tubules Future Ovarian Cortex Primordial Follicles Secondary or Cortical Sex Chords (egg nests)

34. Mullerian Duct Regressing Wolffian Duct Ovarian Cortex Primordial Follicles Ovarian Medulla

35. Development of the Uterus, Cervix and Vagina Mullerian Duct

36. Fused Mullerian Duct Hymen

38. Ovary Regressing Wolffian Duct Mullerian Duct Broad Ligament Development (transverse anterior section) Reproductive tract develops outside the peritoneum!

39. Ovary Regressing Wolffian Duct Mullerian Duct

40. Regressing Wolffian Duct Mullerian Duct Genital Fold (Future Broad Ligament) (Posterior Transverse Section)

41. Testis Determining Factor (SRY gene product) Testes develop Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Degeneration of Mullerian duct Testosterone Development of male duct system XY Male No TDF Ovaries Develop No AMH Mullerian ducts become the oviducts, uterus, cervix and part of the vagina XX Female No Testosterone Degeneration of Wolffian duct

42. Phenotypic Sex

43. Testis Determining Factor (SRY gene product) Testes develop Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Degeneration of Mullerian Duct Testosterone Development of male duct system XY Male Dihydrotestosterone Development of penis scrotum and accessory sex glands

44. Testis T T Nucleus TR Wolffian Duct Cells

45. Testis T T 5  - Reductase D Nucleus DR Accessory Sex Glands * and External Genitalia Cells * Prostate, Cowper’s Gland

46. Significance of DHT Androgen receptor has a higher affinity for DHT Can get effects with low levels of circulating testosterone Secondary sex characteristic tissue in the male expresses 5  -reductase Androgen receptor has a higher affinity for DHT Can get effects with low levels of circulating testosterone Secondary sex characteristic tissue in the male expresses 5  -reductase

47. External Genitalia Differentiation

50. Testis Determining Factor (SRY gene product) Testes develop Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Degeneration of Mullerian duct Testosterone Development of male duct system XY Male No TDF Ovaries Develop No AMH Mullerian ducts become the oviducts, uterus, cervix and part of the vagina XX Female No Testosterone Degeneration of Wolffian duct Dihydrotestosterone Development of penis scrotum and accessory sex glands

51. Brain or Behavioral Sex

52. Brain and Behavioral Sex Differentiation Gonadal Steroid Hormones Brain Structure Sexual Behavior Genetics Experience

53. Brain Sexual Differentiation Rat female –Give testosterone shortly after birth fail to copulate or cycle like female as adult Sexually dimorphic nucleus Human male and female differences in behaviors –aggression –childhood play –3D visual rotation

54. Descent of the Testis into the Scrotum

55. Testicular Descent Fusion of the tunica albuginea and peritoneum to form the visceral tunica vaginalis

56. Front View Spermatic Artery Fusion of Peritoneum and Gubernaculum Gubernaculum Inguinal Ring Peritoneum Testis

57. Visceral Growth Peritoneum Spermatic Artery Gubernaculum (rapid growth) Gubernaculum (rapid growth) Inguinal Ring Peritoneum Testis Visceral Tunica Vaginalis Parietal Tunica Vaginalis Rapid growth of gubernaculum Testis is pulled down to the inguinal ring.

58. Gubernaculum regresses Testis pulled into scrotum

59. Continued regression of Gubernaculum Testis pulled deeper into Scrotum Vaginal Process attaches to Scrotum Space between Visceral and Parietal T.V. is continuous with Peritoneum

60. Failure or Problems With Testicular Descent Cryptorchid –unilateral –bilateral Inguinal Hernia

61. Loop of Intestine

62. Abnormalities in Development

63. The Freemartin in Cattle Female born twin to a bull Extra embryonic membranes fuse to form a common chorion Common blood supply –At time of testis formation –Before ovarian formation Both fetuses share a common hormone milieu –testosterone –anti-mullerian hormone Animals are chimeric (WBC from other twin) –TDF (SRY) expressed in both individuals

64. Freemartin AMH - blocks Mullerian ducts –Posterior vagina, no anterior vagina Ovaries do not grow –SRY expressed from chimeric cells (Ovotestis) –Testosterone produced Clitoral enlargement Bullish behavior - masculinization Use as estrus detector Abnormalities exist as a continuum

65. Testicular Feminization in an XY Individual No androgen receptor Testis No testosterone response so no Wolffian duct development AMH present so mullerian ducts regress External genitalia is female due to lack of androgen

66. 5  Reductase Deficiency in an XY Individual testis AMH present so Mullerian ducts regress some Wolffian ducts psuedovagina and female external genitalia at puberty may differentiate into phenotypic male