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

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

5. Migration from endoderm
through mesoderm.

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

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

8. Development of Mesenephros and Metenephros

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

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

11. 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

12. 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 = 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 gene that controls testicular differentiation is on the Y chromosome in mammals.

13. Human X and Y Chromosomes

14. 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
Causes
primary sex chord (seminiferous tubule) development
Anti-Mullerian Hormone production
Testosterone production
absence of SRY
2nd sex chords (egg nests) develop

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

16. 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

17. Gonadal Sex

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

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

20. Mesonephric Tubules Wolffian Duct Tunica Albuginea
Rete Tubules
Wolffian
Duct
Primary, Epithelial or
Medullary Sex Chords
Primordial germ cells (gonocytes)
Pre-Sertoli Cells
Mullerian Duct
Tunica
Albuginea

21. Primary Sex Chords in Fetal Testis
Pre-Sertoli
Gonocyte

22. Hormonal Sex

23. 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

24. Wolffian Duct Cells
Nucleus T
Testis T TR

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

26. 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

27. Vas efferentia

28. 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

29. Ovarian Development Regressing Tubules Mullerian Duct Primary or
Epithelial
Sex Chords
Future Ovarian
Cortex
Wolffian
Duct

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

31. 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)

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

33. 2nd Sex Chords in Fetal Ovary

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

35. Fused Mullerian
Duct
Hymen

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

38. Ovary
Regressing
Wolffian
Duct
Mullerian
Duct

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

40. 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

41. Phenotypic Sex

42. 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

43. Wolffian Duct Cells
Nucleus T
Testis T TR

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

45. 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

46. External Genitalia Differentiation

49. 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

50. Brain or Behavioral Sex

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

52. 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

53. Descent of the Testis into the Scrotum

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

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

56. 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

57. Gubernaculum regresses Testis pulled into scrotum

58. 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

59. 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

60. Normal Dog Seminiferous Tubule

61. Cryptorchid Dog Seminiferous Tubule
Sertoli Cells

62. 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

63. Inguinal Hernia
Loop of Intestine

64. Abnormalities in Development

65. The Freemartin in Cattle
Female born twin to a bull
Placenta membranes of the 2 fetuses fuse
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

66. Normal

67. Freemartin

68. Normal Vs. Freemartin

69. Freemartin AMH from bull - blocks Mullerian ducts
Posterior vagina, no anterior vagina
Testosterone from bull
clitoral enlargment
Brain changes like that of male
Ovaries do not grow but are chimeric
Ovotestis
SRY and therefore AMH and Testosterone
Further changes and adult male behavior
Use as estrus detector
Abnormalities exist as a continuum

70. 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

71. Testicular Feminization

72. 5 Reductase Deficiency in an XY Individual
Guevedoces (penis at 12)
testis
AMH present so Mullerian ducts regress
Wolffian ducts
psuedovagina and female external genitalia
at puberty may differentiate into more of a phenotypic male

73. Guevedoces Development
Normal tissue dependent upon testosterone is shown in black.