Overexpression of Kdm6b induces testicular differentiation in a temperature-dependent sex determination system

In reptiles, such as the red-eared slider turtle (Trachemys scripta elegans), gonadal sex determination is highly dependent on the environmental temperature during embryonic stages. This complex process, which leads to differentiation into either testes or ovaries, is governed by the finely tuned expression of upstream genes, notably the testis-promoting geneDmrt1and the ovary-promoting geneFoxl2. Recent studies have identified epigenetic regulation as a crucial factor in testis development, with the H3K27me3 demethylase KDM6B being essential forDmrt1expression inT. s. elegans.However, whether KDM6B alone can induce testicular differentiation remains unclear. In this study, we found that overexpression ofKdm6binT. s. elegansembryos induced the male development pathway, accompanied by a rapid increase in the gonadal expression ofDmrt1at 31°C, a temperature typically resulting in female development. Notably, this sex reversal could be entirely rescued byDmrt1knockdown. These findings demonstrate thatKdm6bis sufficient for commitment to the male pathway, underscoring its role as a critical epigenetic regulator in the sex determination of the red-eared slider turtle.