Instead, definitive macrophages are required after sex has been established for ovary-to-testis transformation in response to pathological contexts, like ovarian insufficiency or failure due to mutation of bmp15. In this context, macrophages or macrophage activation by MAFCs expressing Csf1a may be the trigger or respond to the trigger for testis differentiation (Fig. 7). Here, BMP15 is linked to ovarian dysfunction.