Gap junction -mediated cAMP movement between oocytes and somatic cells.

Cyclic AMP (cAMP) plays a critical role in oocyte meiotic maturation. However, the source of cAMP surge prior to maturation and the direction of gap junction-dependent cAMP movement are unclear. In this study, inhibition of gap junctional communication (GJC) using carbenoxolone (3.5 h) induced meiotic resumption in ~90% of follicle-enclosed oocytes (FEOs). The concentration of cAMP in a single oocyte was higher than that in a single cumulus cell, suggesting that the movement of cAMP proceeds from the oocyte to cumulus cells under passive diffusion. The mRNAs of adenylyl cyclases and the corresponding proteins were mainly detected in oocytes. Persistent or transient incubation with forskolin induced meiotic resumption in FEOs. The maturation induced by persistent forskolin treatment was inhibited by carbenoxolone. However, carbenoxolone had no effect on the maturation of FEOs transiently treated with forskolin or persistently treated with follicle-stimulating hormone. Oocyte maturation was inhibited by sequential treatment with carbenoxolone followed by forskolin. The carbenoxolone-induced maturation was accompanied by a cAMP surge, increased PDE3A and MAPK activation, and decreased levels of cGMP and cAMP-dependent PKA I activation.