Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration

Scientists thought for years that the ovariesand testes are fully developed, stable organs that cannot change their structure and function in mature mammals. However, more recent studies have shown that a gene called Foxl2 is active throughout life to prevent ovarycells from becoming more like the Sertoli cellspresent in the testes. Similarly, a gene called Dmrt1 keeps Sertoli cellsfrom becoming more like ovarycells after birth. Scientists don’t yet know all the details about how Dmrt1 prevents testes from becoming more ovary-like. For example, do genes that help testes develop in the embryo (which include two genes called Sox8 and Sox9) play a role in maintainingthe adult testes? Barrionuevo, Hurtado, Kim et al. have now genetically engineeredadult male mice to lack the Sox8 and Sox9genes. The Sertoli cellsin the testes of these mice gradually lost their key characteristics and ultimately died. During this process, the testes cells took on certain characteristics that made them more ovary-like: for example, the ovary- maintainingFoxl2 gene was activated in the Sertoli cells. Eventually, the structures in the testes that produce sperm degenerate and are replaced by empty space in the genetically engineeredmice. This happens because the Sox8 and Sox9genes control the production of proteins that maintainthese structures. In addition, these genes also protect the Sertoli cellsfrom self-destructing, and the testes- maintainingDmrt1 gene is not active when Sox8 and Sox9are missing. More studies are now needed to determine how Sox8 and Sox9work with Dmrt1 to maintainthe testes.