Dose-dependent functions of FGF9 in male primordial germ cell differentiation

Abstract

Primordial Germ Cells (PGCs) are the precursors of gametes. For PGC male differentiation, (i) inhibition of meiosis and (ii) male-inducing factor(s) are essential. It was recently revealed that Fibroblast Growth Factor 9 (FGF9) is one of male-inducing factors. Using isolated PGC culture system, we examined the function of FGF9 in PGC differentiation. We found low FGF9 treatment (0.2 ng/ml) induced PGC male differentiation. Conversely, high FGF9 treatment drastically stimulated PGC proliferation (40%) compared with the control and low FGF9 groups (5~10%). As a result, high FGF9 treatment (25 ng/ml) prevented PGCs to enter the male pathway. Also, we demonstrated that high FGF9 induced ERK1/2 signaling activation for stimulating PGC proliferation while low FGF9 enhanced phosphorylation of p38 signaling to push PGCs into the male pathway.