Specific protein kinase C isoforms α and βI are involved in follicle-stimulating hormone-induced mouse follicle-enclosed oocytes meiotic resumption.

Protein kinase C (PKC) is involved in gonadotrophin-induced oocyte maturation. In the present study, we investigated the role of specific PKC isoforms in the process of follicle-stimulating hormone (FSH)-induced oocyte meiotic resumption. Small antral follicles (200-300 µm in diameter) were isolated from immature mice and cultured in vitro. FSH significantly induced follicle-enclosed oocytes (FEOs) meiotic resumption after 8 hr culture. However, the induced effect of FSH was dose-dependently inhibited by the specific PKC α and βI inhibitor Gö6976, and 100 nM Gö6976 completely blocked FSH function in oocyte meiotic resumption. Furthermore, FSH dramatically induced the expression of transcripts encoding epidermal growth factor (EGF)-like growth factors Areg, Btc, and Ereg mRNA levels, and up-regulated tyrosine phosphorylation level of EGF receptor (EGFR) in granulosa cells. Blocking the function of EGFR by AG1478 eliminated the effect of FSH-induced FEOs meiotic resumption, suggesting that FSH induced oocyte maturation through the activation of EGFR. FSH-induced phosphorylation of EGFR could also be inhibited by Gö6976. Next, we examined the effect of FSH on the expression and phosphorylation PKC α and βI. FSH induced the expression of PKC α at mRNA and protein level, and also up-regulated its phosphorylation level in granulosa cells after 8 hr culture. However, FSH had no effect on the expression of PKC βI but down-regulated its phosphorylation level. In conclusion, FSH-induced activation of PKC α alone, or together with the inactivation of PKC βI in granulosa cells, participates in mouse oocyte meiotic resumption, possibly by the activation of EGFR signaling pathway.