Cortisol induces masculinization of XX medaka through gonadal soma-derived growth factor (GSDF) and anti-Mullerian hormone receptor type 2 (AMHR2)

The medaka Oryzias latipes is a teleost fish with an XX/XY sex determination system similar to that of mammals. However, under high-temperature conditions, XX medaka are masculinized by an elevation of the key teleost glucocorticoid, cortisol. Cortisol inhibits female-type proliferation of germ cells and induces masculinization of XX medaka during gonadal sex differentiation. To identify masculinization mechanisms downstream of cortisol, we analysed the functions of gonadal soma-derived growth factor (gsdf) and anti-Mullerian hormone receptor type 2 (amhr2); these genes are known to play important roles in the inhibition of germ cell proliferation and male differentiation. We investigated the impact of gsdf and amhr2 on the proliferation of germ cells using gsdf knockout (KO) and amhr2 KO medaka. At hatching stage, loss of gsdf or amhr2 function recovered female-type proliferation in germ cells under cortisol treatment. Moreover, cortisol treatment of gsdf KO or amhr2 KO medaka did not induce masculinization of XX medaka. These results suggest that cortisol inhibits female-type proliferation of germ cells and induces masculinization of XX medaka through GSDF and AMHR2. This study thereby provides the first evidence that GSDF and AMHR2 are involved in cortisol-induced masculinization.

Automated summary

This study reveals that cortisol inhibits female-type proliferation of germ cells and induces masculinization of XX medaka through the actions of gonadal soma-derived growth factor (GSDF) and anti-Mullerian hormone receptor type 2 (AMHR2). Loss of GSDF or AMHR2 function under cortisol treatment leads to recovery of female-type proliferation in germ cells and prevents masculinization of XX medaka.