Evaluating the Role of EXOC5 in Early Folliculogenesis

Abstract

Folliculogenesis is the process through which female germ cells (oocytes) develop into viable eggs. This process is reliant on extensive cell- cell communication between oocytes and their surrounding granulosa cells. EXOC5 plays multifaced roles in cell-cell communication, cell signaling, and autophagy. Each wave of folliculogenesis begins when a small subset of the pool of primordial follicles (oocytes with their granulosa cells) are activated to become primary follicles, which then progress to mature follicles to produce viable eggs.Our laboratory has previously determined that EXOC5 is required for folliculogenesis using a Cre-lox system in which ZP3-Cre was used to flox out the Exoc5 only in primary oocytes of primary follicles, to create Zp3-Exoc5-cKO mice. Histological examination of ovaries from these mice revealed that the first wave of folliculogenesis appeared normal at 20 days post-partum (DPP), but all subsequent, adult waves were blocked. This suggested that EXOC5 was not required for the first wave of folliculogenesis but was required for all subsequent waves. However, because the Zp3-Cre is only activated in primary follicles after folliculogenesis has been activated, we created a second conditional knockout mouse, Gdf9-Exoc5-cKO, using Gdf9-Cre, which is activated in the primordial follicle oocytes before folliculogenesis is activated. Histological examination from the ovaries of these mice indicated that in Gdf9-Exoc5-cKO mice, the first wave of folliculogenesis also appears normal, verifying that the first wave of folliculogenesis does not depend on EXOC5. In Zp3-Exoc5-cKO mice, there were no antral follicles present by 60 DPP but primary follicles were plentiful. In Gdf9-Exoc5-cKO mice, however, by 60 DPP, there are no follicles at all, suggesting a more rapid progression to complete infertility when Exoc5 is deleted early.