Humans have forty-six chromosomes, including two sex chromosomes, XX in females and XY in males. It is obvious that the Y chromosome must carry at least one essential gene which determines testicular formation. A gene in the sex-determining region of the short arm of the Y, now referred to as SRY, has been found to direct production of a protein which binds to DNA, inducing differentiation of cells derived from the genital ridges into testes.
Early in fetal life, germ cells migrate from structures known as yolk sacs to the genital ridge. By week 6, undifferentiated gonads consist of germ cells, supporting cells, and steroidogenic cells.
In a male, SRY and other genes induce differentiation of supporting cells into Sertoli cells and steroidogenic cells into Leydig cells to form testes, which become microscopically identifiable and begin to produce hormones by week 8. Germ cells become spermatogonia.Without SRY, ovaries form during months 2-6. Failure of ovarian development in 45,X girls (Turner syndrome) implies that two functional copies of several Xp and Xq genes are needed. Germ cells become ovarian follicles. Supporting and steroidogenic cells become theca cells and granulosa cells, respectively.
In a male fetus, testes produce steroid and protein hormones essential for internal and external anatomic differentiation. Leydig cells begin to make testosterone by the end of month 2 of gestation. Antimullerian hormone (AMH) is a protein hormone produced by Sertoli cells from the 8th week on. AMH suppresses development of müllerian ducts in males, preventing development of a uterus.
Fetal ovaries produce estradiol, which supports follicular maturation but plays little part in other aspects of prenatal sexual differentiation, as maternal estrogen floods fetuses of both sexes.
Gonads are histologically distinguishable by 6–8 weeks of gestation. A fetus of that age has both mesonephric (wolffian) and paramesonephric (mullerian) ducts. Subsequent development of one set and degeneration of the other depends on the presence or absence of two testicular hormones: testosterone and AMH.Local testosterone causes each wolffian duct to develop into epididymis, vas deferens, and seminal vesicles. Without male testosterone levels, wolffian ducts degenerate and disappear. Müllerian ducts develop into a uterus, fallopian tubes, and upper vagina unless AMH induces degeneration.