The signaling pathways leading to female development are not well known in many animal species, probably because development of embryos into females was traditionally considered the default developmental pathway.

Recently, in a study published in Proceedings of the National Academy of Sciences (PNAS), a research group led by Prof. DU Weiguo from the Institute of Zoology, Chinese Academy of Sciences uncovers the transcription factor pSTAT3 initiating female pathway underlying temperature-dependent sex determination.

The research group studied the molecular mechanisms of sex determination in the red-eared slider turtle with temperature-dependent sex determination (TSD), in which embryos develop into males if incubated at 26 °C and into females if incubated at 31 °C.

Firstly, the researchers found that the expression level of the transcription factor pSTAT3 and the sex-determining gene FoxI2 was temperature-dependent and differed between sexes. Secondly, they revealed that inhibition and activation of pSTAT3 led to female-to-male or male-to-female sex reversal in embryos at the female-producing temperature of 31 °C or male-producing temperature of 26 °C, respectively. Nonetheless, the sex reversal of these embryos can be rescued by knocking down or overexpressing FoxI2, respectively. Finally, the researchers discovered that pSTAT3 directly binds to the promoter locus of FoxI2 and thereby initiates the female pathway.

“This is the first time to establish a direct genetic link between warm-temperature-induced STAT3 phosphorylation and female pathway initiation in a TSD system” said the first author Dr. WU Pengfei.

More importantly, these findings provide a mechanistic explanation of sex determination in fluctuating temperatures, which is actually a result of the antagonism between male and female signals rather than the default female outcome.

Paper link: https://doi.org/10.1073/pnas.2401752121

Figure 1. A diagram of temperature-dependent female-determining pathway in T. scripta.

（Image from WU Pengfei）