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

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

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

8. Migration from endoderm
through mesoderm.

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

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

11. Development of Mesenephros and Metenephros

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

13. Paramesonephric Ducts
Jost Experiments
Mesonephric Ducts
(Wolffian Ducts)
Paramesonephric Ducts
(Mullerian Ducts)
Testis
Ovary
Epididymis
Oviduct
Epididymis
Vas Deferens
Seminal Vesicles
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

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
Short arm of Y chromosome
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

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

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

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

24. Hormonal Sex

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

26. Wolffian Duct Cells
Nucleus T
Testis T TR

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

28. Testis Determining Factor
XY Male
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

29. Vas efferentia

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

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

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

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

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

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

36. Fused Mullerian
Duct
Hymen

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

39. Ovary
Regressing
Wolffian
Duct
Mullerian
Duct

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

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

42. Phenotypic Sex

43. XY Male 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
Dihydrotestosterone
Development of penis
scrotum and accessory
sex glands
Development of male
duct system

44. Wolffian Duct Cells
Nucleus T
Testis T TR

45. Accessory Sex Glands* and External Genitalia Cells
Nucleus T
Testis T D DR
5-
Reductase
*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 5a-reductase

47. External Genitalia Differentiation

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

51. Brain or Behavioral Sex

52. Brain and Behavioral Sex Differentiation
Genetics
Gonadal Steroid Hormones
Sexual Behavior
Brain Structure
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. albuginea and peritoneum to form the visceral tunica vaginalis
Testicular Descent
Fusion of the tunica
albuginea and peritoneum
to form the visceral tunica vaginalis

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

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

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 - highly heritable
Unilateral or bilateral
Germ cells fail to multiply and then die, sertoli cells only in seminferous tubules
High percentage develop testicular cancer
Surgical correction possible but does not reduce cancer risk

61. Normal Dog Seminiferous Tubule

62. Cryptochid Dog Seminiferous Tubule

63. Failure or Problems With Testicular Descent
Cryptorchid - highly heritable
Unilateral or bilateral
Germ cells fail to multiply and then die, sertoli cells only in seminferous tubules
High percentage develop testicular cancer
Surgical correction possible but does not reduce cancer risk
Inguinal Hernia

64. Inguinal Hernia
Loop of Intestine

65. Abnormalities in Development

66. 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

67. Freemartin AMH - blocks Mullerian ducts Ovaries do not grow
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

68. 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

69. 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