Molecular mechanisms underlying female sex determination--antagonism between female and male pathway.

Molecular interactions in a developing gonad are crucial for an individual since they determine its phenotypic sex. The process of sex determination is complicated because of the antagonistic interactions between the male and female pathway. Factors responsible for the determination of femaleness make the female pathway. This pathway has to inhibit a complex network of male-determining factors and also has to induce the expression of genes that drive differentiation of the ovary. Morphological description of the ovary development suggests that this process is simple, however, the analysis of the robust gene expression indicates that genetic control of the ovary differentiation is active and complicated at the molecular level. A plethora of genes is expresed in developing gonads. Nevertheless, there are only a couple of genes the role in ovary development of which has been described till now. RSPO1 seems the main gene participating in the establishment of the ovary fate. The loss of functional R-spondin1 causes the complete female-to-male sex reversal in human. The second important factor is WNT4 which plays an opposite role to R-spondin1 in the gonad but also is decisive for the ovarian fate. WNT4 and RSPO1 drive the disposition of beta-catenin in cells and thus these factors regulate gene transcription and cell-cell adhesion. Foxl2 is another gene contributing to the development of the ovary. In females also germ cells seem to play important role in sex determination.