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=== Differentiation of the Testis === * '''<span style="color:#ff0000">Gonads are first identified at 32 days (≈4.5 weeks)''' in humans. ** '''<span style="color:#ff0000">At this sexually indifferent stage, the gonads and the internal and external genitalia are identical in males and females.''' ** '''<span style="color:#ff0000">Gonadal determination involves separate genetic pathways for development of testis and ovary.''' *** '''<span style="color:#ff0000">SRY (sex-determining region on the Y chromosome) is a master switch in males that regulates downstream testis-determining genes.''' * '''<span style="color:#ff0000">By 6 weeks’ gestation, primordial germ cells</span>''' migrate from the yolk sac and '''<span style="color:#ff0000">differentiate into gonocytes</span>''' * '''<span style="color:#ff0000">In males, expression of SRY begins at 41 to 44 days (≈6 weeks) followed by the histologic appearance of Sertoli cells''' ** '''<span style="color:#ff0000">SRY expression in the indifferent gonad triggers testicular development.''' ** SRY is important for Sertoli cell specification, but downstream testis-determining genes are required for Sertoli cell differentiation and proliferation * '''<span style="color:#ff0000">Fetal Sertoli cells produce anti-müllerian hormone (AMH) (also called müllerian inhibiting substance [MIS]) soon after they differentiate''' ** Fetal and early postnatal Sertoli cells lack androgen-receptor expression. *** Precense of androgen-receptor on Sertoli cells would allow inappropriate androgen-induced inhibition of AMH production and precocious stimulation of spermatogenesis. ** '''<span style="color:#ff0000">The process of müllerian regression occurs at 9 to 10 weeks''' *** The early development of the external genitalia in the two sexes is relatively similar before the 9th week of gestation. ** '''AMH levels remain high during childhood and are downregulated at puberty.'''
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