Genetics of sex determination: exceptions that prove the rule.

The dogma that male and female embryos develop in identical fashion until SRY initiates Sertoli cell differentiation in the hitherto bipotential gonad is in need of reevaluation in the light of data that do not fit into this scheme. One of the exceptions that proves the rule of sex determination is true hermaphroditism, the existence of individuals with both testicular and ovarian tissue. Furthermore, the two types of tissues are asymmetrically distributed, ovaries being more common on the left side and testes and ovotestes on the right. Hermaphrodite mice also exhibit bilateral asymmetry of gonad differentiation, but in the opposite direction: ovaries on the right, testes and ovotestes on the left. To explain these asymmetries, it is necessary to consider the relationship between growth and gonadal differentiation. The idea that accelerated growth precedes histological differentiation of the testis has recently been confirmed by the finding that Sry induces cell proliferation in fetal mouse gonads, suggesting that the differentiation of Sertoli cells may be dependent on a critical cell number. Recent evidence has also shown that XY embryos develop faster than their XX counterparts at very early stages of development, and it has been reported that SRY and ZFY are expressed in early human and murine embryos. The relationship between growth and sex differentiation links the mammalian system with those of nonmammalian vertebrates with temperature-dependent sex determination. Early growth differences between male and female human embryos question the belief that all sex differences in later life are due to gonadal hormones. Copyright 2000 Academic Press.