Endocrine Abstracts

Meiotically arrested mammalian oocytes are stimulated to resume meiosis by LH. This response is associated with interruption of gap junctional communication (GJC) within the ovarian follicle and can be reversed by elevation of intraoocyte cAMP. In the present study, we examined the hypothesis that termination of cellular communication in the ovarian follicle is sufficient for induction of oocyte maturation. To test our hypothesis we used rat follicle-enclosed oocytes (FEO) that remain meiotically arrested when incubated under control condition and are stimulated to resume meiosis by LH. We found that the addition of carbenoxolone (CBX, 100 mM, 5 hrs) promoted maturation of almost all the oocytes, a response that was also obtained by a transient (two hours) exposure to this blocker of GJC. CBX-induced oocyte maturation was associated with a substantial decrease in intraoocyte concentrations of cAMP and was blocked by the phosphodiesterase inhibitor, isobuterymethylanthine (IBMX). Unlike LH, CBX did not activate MAPK in the follicular cells and inhibition of the MAPK signaling pathway by UO126, did not prevent the resumption of meiosis. Injection of CBX (100 mM) into the ovarian bursa of intact animals stimulated maturation in 30% of the oocytes whereas no maturation was observed in the contralateral ovary injected with PBS. We conclude that since breakdown of communication within the ovarian follicle is associated with a drop of intraoocyte cAMP concentrations and results in resumption of meiosis, this could be the physiological mechanism employed by LH for the induction of oocyte maturation.