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Genital System

The other genes involved in gender differentiation

Despite the overriding importance of the SRY gene for gender differentiation, certain abnormalities have shown that still other genes on the X chromosome as well as on certain autosomes (9, 11, 17, and 19) are involved and appear to be just as important for gonadogenesis. They intervene before and after the activation of the SRY gene.

Illustration
Schematic diagram of the molecular factors involved in the development of the genital apparatus.

The following genes have been identified:

  • In the mouse, the WT1 gene (chromosome 11) is expressed in the urogenital ridge, in the cells that come from the mesonephros, the supporting cells (Sertoli) and the follicular cells of the ovary. This gene is required for the morphogenesis of the urogenital system and represents a regulation gene for the transcription of the SRY. It has been found in patients with a Wilms' tumor. Wilms' tumor is a renal disorder of embryonic origin that is characterized by an uncontrolled proliferation of the metanephric blastema. A mutation of a single copy of the WT1 gene, which is accompanied by a functional failure of this gene, hinders gonadogenesis

  • The gene expression of the SOX9 gene (chromosome 17), which in the mouse is found in the genital ridge of both sexes and in the supporting cells (Sertoli), plays a role in the activation of the AMH gene (antimüllerian hormone). The mutation with a functional failure of a single copy of the SOX9 gene leads to a reversal of the gender of a male individual (46,XY).

  • The SF1 gene (chromosome 9), which in the mouse is expressed in the gonad anlagen of both sexes, activates the expression of the gene for the synthesis of steroids.

  • The DAX1 gene (chromosome X), which is also expressed in the genital ridges, hinders the activation of SF1. An excessive expression of DAX1 hinders a differentiation of the testes. A duplication (DAX1) leads to a reversal of the sex of a male individual (46, XY).

  • The gene coding for AMH (antimüllerian hormone; chromosome 19), which in the mouse is expressed in the supporting cells (Sertoli), is responsible for the atrophy of the paramesonephric duct (Müller). Its expression is nevertheless dependent on the united action of several genes (SF1, SOX9 and DAX1).