FGF receptor 2 signaling in granulosa cells is required for normal female fertility in mice

In brief: Fibroblast growth factor (FGF) signaling has been implicated in ovarian follicular development in mammals, but its in vivo role in female fertility remains unclear. This study reveals the requirement of fibroblast growth factor receptor 2 (FGFR2) signaling in ovarian granulosa cells for normal female fertility in mice, likely by regulating glycolysis in cumulus cells and enhancing oocyte developmental competence. Abstract: FGF signaling has been implicated in ovarian follicular development in mammals, but its in vivo role in female fertility remains unclear. To investigate this role, we generated granulosa cell-specific conditional knockout (cKO) mice lacking FGF receptor 2 (FGFR2). Fgfr2 cKO female mice exhibited significantly reduced fertility despite normal follicular development, estrous cycles, and ovulation. In contrast, cumulus cells in cKO mice showed decreased expression of glycolytic enzymes such as PFKP and LDHA, potentially impairing metabolic support for oocytes. Consequently, cKO cumulus cells were less competent than control cells in supporting the meiotic resumption of oocytes under in vitro conditions. Furthermore, while cKO oocytes developed into blastocysts at normal rates in vitro, their ability to reach term after embryo transfer was significantly diminished. These findings demonstrate that FGFR2-mediated FGF signaling in granulosa cells is essential for normal female fertility, likely by regulating glycolysis in cumulus cells and promoting oocyte developmental competence.