Role of in the Regulation of Apoptosis and Cell Cycle in Rat Granulosa Cells during the Periovulatory Period.

In the ovary, the luteinizing hormone (LH) surge suppresses the proliferation and induces the luteinization of preovulatory granulosa cells (GCs), which is crucial for the survival of terminally-differentiated GCs. () has been shown to play a role in regulating the cell cycle and apoptosis in various cell types. The rapid induction of expressions by LH was observed in preovulatory GCs. To evaluate whether affects GC proliferation and survival, primary rat GCs were isolated from pregnant mare serum gonadotropin-primed Sprague⁻Dawley rat ovaries and transfected with a expression vector or -specific siRNA, followed by determination of the transcript levels of apoptosis-related and cell cycle-related genes. Cell proliferation, viability, and apoptosis were analyzed by BrdU incorporation, a Cell Counting Kit-8 assay, a bioluminescence caspase 3/7 assay, and flow cytometry. LH treatment increased mRNA expression in preovulatory GCs. Transcripts of () and cell cycle promoters ( and ) decreased, whereas those of the cell cycle inhibitor, , increased. Altering the expression of by overexpression or knockdown consistently affected the expression of and . In agreement with this, overexpression reduced cell viability, increased the fraction of apoptotic cells, and arrested cell cycle progression in G1 phase. We conclude that increases the susceptibility of preovulatory GCs to apoptosis by down-regulating , and promotes LH-induced cell cycle exit. It appears to be a key regulator induced by the LH surge that determines the fate of GCs in preovulatory follicles during the luteal transition.