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

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

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

Migration from endoderm through mesoderm.

In birds the migration is via the blood stream.

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

Development of Mesenephros and Metenephros

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

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

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

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

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.

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

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

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

Gonadal Sex

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

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

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

Hormonal Sex

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

Testis T T Nucleus TR Wolffian Duct Cells

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

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

Vas efferentia

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

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

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

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

Mullerian Duct Regressing Wolffian Duct Ovarian Cortex Primordial Follicles Ovarian Medulla

Development of the Uterus, Cervix and Vagina Mullerian Duct

Fused Mullerian Duct Hymen

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

Ovary Regressing Wolffian Duct Mullerian Duct

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

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

Phenotypic Sex

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

Testis T T Nucleus TR Wolffian Duct Cells

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

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

External Genitalia Differentiation

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

Brain or Behavioral Sex

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

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

Descent of the Testis into the Scrotum

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

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

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.

Gubernaculum regresses Testis pulled into scrotum

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

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

Loop of Intestine

Abnormalities in Development

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

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

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

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