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

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

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

Migration from endoderm through mesoderm.

In birds the migration is via the blood stream.

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

Development of Mesenephros and Metenephros

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

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

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 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

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

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

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

Hormonal Sex

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

Wolffian Duct Cells Nucleus T Testis T TR

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

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

Vas efferentia

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

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

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

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)

Primordial Follicles Mullerian Duct Ovarian Medulla Ovarian Cortex Regressing Wolffian Duct

Development of the Uterus, Cervix and Vagina Mullerian Duct

Fused Mullerian Duct Hymen

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

Ovary Regressing Wolffian Duct Mullerian Duct

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

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

Phenotypic Sex

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

Wolffian Duct Cells Nucleus T Testis T TR

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

External Genitalia Differentiation

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

Brain or Behavioral Sex

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

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

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

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

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 - 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

Normal Dog Seminiferous Tubule

Cryptochid Dog Seminiferous Tubule

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

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 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

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