FOSL2 Directly Regulates FSHR and CYP11A1 Transcription: An Essential Transcription Factor for Gonadotropin-Dependent Folliculogenesis

Fosl2, a member of the AP-1 family, has been widely studied in the fields of tumorigenesis and immune response, but its role in folliculogenesis remains unclear. In this investigation, we presented comprehensive in vitro and in vivo evidence to precisely define the biological functions of Fosl2 in folliculogenesis. Fosl2 in both mouse and sheep, we demonstrated that the knockdown of Fosl2 effectively inhibited cell proliferation and promoted cell apoptosis in both primary GCs and the GCs of cultured gonadotropin (GTH)-dependent follicles. To explore the in-vivo function of Fosl2, we generated an ovarian GC-specific conditional knockout (CKO) mouse model. CKO mice showed impaired GTH-dependent folliculogenesis, leading to disrupted estrous cycles and infertility in female mice. Subsequent bioinformatics analysis and experimental results indicated that Fosl2 regulates the transcription of FSHR and CYP11A1. These findings unveiled the essential role of Fosl2 in governing the development of GTH-dependent folliculogenesis, thereby providing a novel strategy for elucidating GTH-dependent folliculogenesis mechanisms and treating ovarian dysfunction.