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A new look at the mechanisms controlling sex differentiation in mammals.

The testis appears to be the sex differentiator in the fetus. Castration of male or female rabbit fetuses results in a female genital tract. The male testis has a repressive effect on the Mullerian duct formation and possesses a masculinizing hormone. Antiandrogens administered during fetal development produce testicular feminization. The Mullerian ducts are absent in such experiments indicating antiandrogens are without effect on the testicular Mullerian inhibitor. The testis also imposes both prenatally and neonatally sexual differentiation effects on the nervous system apparent only in adulthood. Testicular organization rapidly becomes discernible in the male fetus while the presumptive ovaries remain undifferentiated gonadal primordium. The processes which impose early testicular organization are still unknown as are the factors leading to ovarian differentiation. When 2 or more twin fetuses are present in a pregnant cow if at least 1 male is present most of the females become sexually abnormal. Ovaries are usually stunted and seminiferous tubules may be present. Fetuses may exchange blood cells and fetal hormones through fused fetal membranes. In observations made on freemartin fetuses: 1) at 40-48 days gestation testicular development is seen; 2) at 49-52 days normal females are without much change while in freemartins Mullerian ducts decrease as in males; 3) at 53-60 days male characteristics become obvious females show little change and freemartins are without masculine characteristics but ovarian growth is inhibited. Organogeneti c processes still are possible in the freemartin gonad at late developmental stages. It would appear that some factor in the freemarti n both inhibits the growth of the outer part of the gonads and induces the retrogression of the upper Mullerian ducts. The extent of our ignorance concerning some of the major mechanisms controlling sex differentiation is a challenge to incite new research in a field important to biologists as well as clinicians.