Significance of DHT External Genitalia Differentiation

• 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 5α-reductase

Testis Determining Factor (SRY gene product) No TDF XY Male XX Female

Testes develop Develop

Sertoli cells secrete No No AMH anti-mullerian hormone (AMH) Testosterone Brain or Behavioral Sex

AMH causes leydig Degeneration of cells to differentiate Mullerian duct Degeneration of Mullerian ducts Wolffian duct become the oviducts, uterus, cervix Testosterone Dihydrotestosterone and part of the

Development of penis Development of male and accessory duct system sex glands Brain and Behavioral Sex Differentiation Brain Sexual Differentiation

Genetics • Rat female » Give testosterone shortly after birth fail to copulate or cycle like female as Gonadal Sexual – Brain adult Steroid Structure Behavior Hormones • Sexually dimorphic nucleus

Experience • Human male and female differences in behaviors » aggression » childhood play » 3D visual rotation

Testicular Descent

Fusion of the tunica albuginea and Descent of the Testis to form the visceral into the Scrotum

Rapid growth of Spermatic Artery Front View Spermatic Artery Peritoneum

Visceral Growth Visceral Growth Fusion of Peritoneum Inguinal Ring and Testis Testis Gubernaculum Peritoneum Gubernaculum Gubernaculum (rapid growth) Parietal Tunica Vaginalis Peritoneum Testis is pulled down Visceral Tunica Inguinal Ring to the inguinal Vaginalis ring. Gubernaculum Spermatic Artery Spermatic Artery regresses Continued regression of Peritoneum Peritoneum Gubernaculum Visceral Growth Visceral Growth Testis pulled deeper Inguinal Canal into Scrotum Peritoneum Peritoneum Testis Vaginal Vaginal Process attaches to Scrotum Process Gubernaculum (Regressing) Testis Parietal Tunica Space between Parietal Tunica Vaginalis Vaginalis Visceral and Parietal T.V. is continuous with Testis pulled into Visceral Tunica Peritoneum Visceral Tunica Vaginalis scrotum Vaginalis Gubernaculum (Fully Regressed)

Failure or Problems With Normal Dog Seminiferous Tubule 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

Failure or Problems With Cryptorchid Dog Seminiferous Tubule Testicular Descent •Cryptorchid - highly heritable –Unilateral or bilateral •Germ cells fail to multiply and then die, sertoli cells only in seminferous tubules Sertoli Cells –High percentage develop testicular cancer –Surgical correction possible but does not reduce cancer risk

• Inguinal Hernia

Loop of Intestine

Abnormalities in Development

The Freemartin in Cattle Normal • 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

Freemartin Normal Vs. Freemartin Freemartin Testicular Feminization in an XY Individual • AMH from bull - blocks Mullerian ducts » Posterior vagina, no anterior vagina • No androgen receptor

• Testosterone from bull • Testis » clitoral enlargment » Brain changes like that of male • No testosterone response so no Wolffian duct • Ovaries do not grow but are chimeric development » Ovotestis – SRY and therefore AMH and Testosterone • AMH present so mullerian ducts regress – Further changes and adult male behavior

• Use as estrus detector • External genitalia is female due to lack of androgen • Abnormalities exist as a continuum

5α Reductase Deficiency in an XY Individual • Guevedoces (penis at 12)

• Testis Testicular Feminization • 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.