Granulosa cell expression of Fos is critical for regulating ovulatory gene expressions in the mouse ovary
A previous study showed that female Fos null mice fail to ovulate even when given gonadotropins, suggesting that ovarian expression of Fos is critical for successful ovulation. However, the expression of FOS and function of FOS have not been determined in the mouse ovary. FOS, a member of the Fos family (Fos, Fosb, Fosl1, and Fosl2), functions as a transcription factor by forming a heterodimer complex with a member of Jun family (Jun, Junb, and Jund). The present study demonstrated rapid increases in Fos, along with other Fos and Jun family members, after hCG administration in the ovary of immature PMSG-primed mice and after the LH surge of naturally cycling animals. ChIP-seq analysis identified 1965 FOS-binding genes in granulosa cells collected at 3h post-hCG, including Pgr, Ptgs2, Tnfiap6, and Edn2, genes known to be involved in the ovulatory process. When super-ovulation was induced, the number of oocytes released was significantly reduced in Esr2cre/+ - driven granulosa cell-specific Fos knockout (gcFosKO) mice. This reduction was accompanied by lower expression of Pgr, Ptgs2, Ptgs1, and Edn2 in preovulatory follicles of gcFosKO mice compared to those in control litter mates. In addition, gcFosKO mice showed a trend of decreasing average litter size. Together, this study provided a comprehensive characterization of the tightly controlled up-regulation of all Fos and Jun family members in mouse preovulatory follicles after the LH surge or ovulatory hCG administration and revealed FOS's role in regulating the expression of key ovulatory genes in the mouse ovary. Overall design: in vivo 3 h post-human chorionic gonadatropin (hCG) injection granulosa cells collected from female mice ChIP-Seq with FOS antibody (Santa Cruz, sc-7202, I1012)