Animal Science 434 Reproductive Physiology Lec 5 Embryogenesis
Animal Science 434 Reproductive Physiology Lec 5: Embryogenesis of the Pituitary and Sexual Development
Development of the Pituitary Gland Infundibulum Brain Stomodeum Rathke’s Pouch
Germ Cell 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 • » regresses » portions of reproductive tract Metenephros » Adult kindney and urinary ducts
Development of Mesenephros and Metenephros
Jost Experiments Mesonephric Ducts Paramesonephric Ducts (Wolffian Ducts) (Mullerian Ducts) Ovary Testis Epididymis Oviduct Uterus Epidi Vas Deferens dymis Seminal Vesicles
Sex Determination: The Jost Paradigm Chromosomal Sex Gonadal Sex Hormonal Sex Phenotypic Sex Brain and/or Behavioral Sex
Chromosomal Sex • Single Pair of sex chromosomes • Sex is environmentally determined • Multiple sex chromosomes • Haplodiploidy » mammals, some but not all vertebrates » sea worms, fish, reptiles » invertebrates, insects, reptiles » bees, spiders
Chromosomal Sex A. Drosophila • Sex depends on the number of X chromosomes – X or XY or XO = Male – XX or XXY = Female B. Human (mammals) • XY or XXYY or XXXY = Male (testis) • XX or XXX = Female (ovary) • XO = Female with incomplete ovarian development • XXY or XXYY or XXXXY = testis but impaired sperm production C. Conclusion • The gene that controls testicular differentiation is on the Y chromosome in mammals.
Human X and Y Chromosomes
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 • 2 nd 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
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 Rete Tubules Wolffian Duct Mullerian Duct Primary, Epithelial or Medullary Sex Chords Tunica • Primordial germ cells Albuginea (gonocytes) • Pre-Sertoli Cells
Primary Sex Chords in Fetal Testis Pre-Sertoli Gonocyte
Hormonal Sex
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 Testis T T TR
Efferent Ducts Rete Tubules (Vas Efferentia) Epididymis Vas Deferens Tunica Albuginea Seminiferous Tubules
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 Degeneration of Mullerian duct
Vas efferentia
Female Development XX Female No TDF Testes Determining Factor Ovaries Develop No Testosterone Wolffian Ducts Regress No AMH Mullerian ducts become the oviducts, uterus, cervix and part of the vagina
Ovarian Development Regressing Tubules Mullerian Duct Primary or Epithelial Sex Chords Future Ovarian Cortex Wolffian Duct
Regressing Tubules Mullerian Duct Regressing Epithelial Sex Chords Future Ovarian Cortex Regressing Wolffian Duct
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 Regressing Wolffian Duct Ovarian Cortex
2 nd Sex Chords in Fetal Ovary
Development of the Uterus, Cervix and Vagina Mullerian Duct
Fused Mullerian Duct Hymen
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) Genital Fold (Future Broad Ligament) Regressing Wolffian Duct Mullerian Duct
Testis Determining Factor (SRY gene product) XY Male Testes develop Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Testosterone Development of male duct system Degeneration of Mullerian duct No TDF XX Female Ovaries Develop No Testosterone Degeneration of Wolffian duct No AMH Mullerian ducts become the oviducts, uterus, cervix and part of the vagina
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 male duct system Development of penis scrotum and accessory sex glands
Wolffian Duct Cells Nucleus Testis T T TR
Accessory Sex Glands* and External Genitalia Cells Nucleus Testis T T D 5 Reductase DR *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
External Genitalia Differentiation
Testis Determining Factor (SRY gene product) XY Male No TDF XX Female Testes develop Ovaries Develop No Testosterone Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Degeneration of Mullerian duct Degeneration of Wolffian duct Testosterone Dihydrotestosterone Development of male duct system Development of penis scrotum and accessory sex glands No AMH Mullerian ducts become the oviducts, uterus, cervix and part of the vagina
Brain or Behavioral Sex
Brain and Behavioral Sex Differentiation Genetics Gonadal Steroid Hormones Brain Structure Experience Sexual Behavior
Brain Sexual Differentiation • • • Rat female » Give testosterone shortly after birth – fail to copulate or cycle like Sexually dimorphic nucleus female as adult Human male and female differences in behaviors » » » aggression childhood play 3 D 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 Fusion of Peritoneum and Gubernaculum Spermatic Artery Testis Gubernaculum Peritoneum Inguinal Ring
Rapid growth of gubernaculum Spermatic Artery Peritoneum Visceral Growth Testis Gubernaculum (rapid growth) Testis is pulled down to the inguinal ring. Visceral Growth Inguinal Ring Peritoneum Parietal Tunica Vaginalis 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 – Germ or bilateral 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
Cryptorchid Dog Seminiferous Tubule Sertoli Cells
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 Placenta membranes of the 2 fetuses fuse Common blood supply • Both fetuses share a common hormone milieu • » At time of testis formation » Before ovarian formation » testosterone » anti-mullerian hormone Animals are chimeric (WBC from other twin) » TDF (SRY) expressed in both individuals
Normal
Freemartin
Normal Vs. Freemartin
Freemartin • AMH from bull - blocks Mullerian ducts • Testosterone from bull » Posterior vagina, no anterior vagina » clitoral enlargment » Brain changes like that of male • Ovaries do not grow but are chimeric • • Use as estrus detector Abnormalities exist as a continuum » Ovotestis – SRY and therefore AMH and Testosterone – Further changes and adult male behavior
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
Testicular Feminization
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
Guevedoces Development Normal tissue dependent upon testosterone is shown in black.
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