CAMP inhibits mitogen-activated protein (MAP) kinase activation and resumption of meiosis, but exerts no effects after spontaneous germinal vesicle breakdown (GVBD) in mouse oocytes.

Abstract

Various signaling molecules have been implicated in the oocyte G2/MII transition, including protein kinase C (PKC), cAMP and mitogen-activated protein (MAP) kinases. However, the cross-talk among these signaling pathways has not been elucidated. The present study demonstrates that both germinal vesicle break down (GVBD) and MAP kinase phosphorylation (activation) are inhibited when intraoocyte cAMP is increased by treating the GV-intact oocytes with dibutyryl cyclic AMP (dbcAMP), forskolin, or isobutylmethylxanthine (IBMX). Okadaic acid, a specific inhibitor of protein phosphatase-1 and -2A, completely overcame this effect. Calphostin C, a specific inhibitor of PKC, accelerated both GVBD and MAP kinase phosphorylation, and this effect was attenuated by increased intraoocyte cAMP, whereas PKC activation inhibited these events. Once GVBD occurred, the progression of oocyte maturation and MAP kinase phosphorylation were independent of cAMP These results indicate that an increase in intraoocyte cAMP, in synergy with PKC activation, initiates a cascade of events resulting in inhibition of MAP kinase phosphorylation and GVBD in the mouse oocyte.