Mechanisms of disease: normal and abnormal gonadal development and sex determination in mammals

Sex differentiation in mammels occur in three steps. The first is the establishments of chromosomal sex at fertilization, followed by the differentiation of the gonad into an ovary or testis, and finally the establishment of the phenotypic sex of the embryo and adult, which is regulated by the gonad. Distruption of any of these sages gives rise to sexual ambiguities that include 46,XY pure gonadal dysgenesis, 46,XX true hermaphroditism, and variable degrees of intersexuality. In this review, we focus on the development of the mammalian gonad from a bipotential primordium that differentiates into either an ovary or a testis. We describe the recent increase in our knowledge of the genetic defects that directly affect gonadal development, sex determination, and sex differentiation, with emphasis on the comparision of genetic studies in mice with studies of naturally occuring mutations in humans.