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

Various signaling molecules have been implicated in the oocyte G2/MII trans ition, 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 vesi cle break down (GVBD) and MAP kinase phosphorylation (activation) are inhib ited when intraoocyte cAMP is increased by treating the GV-intact oocytes w ith dibutyryl cyclic AMP (dbcAMP), forskolin, or isobutylmethylxanthine (IB MX). Okadaic acid, a specific inhibitor of protein phosphatase-l and -2A, c ompletely overcame this effect. Calphostin C, a specific inhibitor of PKC, accelerated both GVBD and MAP kinase phosphorylation, and this effect was a ttenuated by increased intraoocyte cAMP, whereas PKC activation inhibited t hese events. Once GVBD occurred, the progression of oocyte maturation and M AP kinase phosphorylation were independent of cAMP. These results indicate that an increase in intraoocyte cAMP, in synergy with PKC activation, initi ates a cascade of events resulting in inhibition of MAP kinase phosphorylat ion and GVBD in the mouse oocyte.