SOX Genes and Their Role in Disorders of Sex Development.

SOX genesare master regulatory genes controlling development and are fundamental to the establishment of sex determination in a multitude of organisms. The discovery of the master sex-determining gene SRY in 1990 was pivotal for the understanding of how testis development is initiated in mammals. With this discovery, an entire family of SOX factors were uncovered that play crucial roles in cell fate decisions during development. The importance of SOX genes in human reproductive development is evident from the various disorders of sex development (DSD) upon loss or overexpression of SOX gene function. Here, we review the roles that SOX genes play in gonad development and their involvement in DSD. We start with an overview of sex determination and differentiation, DSDs, and the SOX gene family and function. We then provide detailed information and discussion on SOX genes that have been implicated in DSDs, both at the gene and regulatory level. These include SRY, SOX9, SOX3, SOX8, and SOX10. This review provides insights on the crucial balance of SOX gene expression levels needed for gonad development and maintenance and how changes in these levels can lead to DSDs.
(© 2022 S. Karger AG, Basel.)