Adenosine reverses calcium-dependent inhibition of follicle-stimulating hormone action and induction of maturation in cumulus-enclosed rat oocytes.

Previous studies indicate that an increase in calcium in the oocyte-cumulus complex (OCC) appears to be associated with induction of oocyte maturation. In contrast, we previously showed that adenosine augments FSH inhibition of maturation in isolated rat OCC. The objective of the present studies was to assess whether adenosine may inhibit calcium-induced oocyte maturation in rat OCC. Two calcium ionophores (A23187 and ionomycin) were used for these studies. In the intact OCC, both ionophores inhibited FSH-stimulated cAMP accumulation and stimulated germinal vesicle breakdown when spontaneous maturation was inhibited by FSH, but the ionophores had no effect when maturation was inhibited by Bu2 cAMP. In contrast, adenosine amplified FSH-sensitive cAMP accumulation and augmented FSH inhibition of oocyte maturation in the intact OCC. Moreover, adenosine reversed ionophore-dependent inhibition of cAMP accumulation and ionophore induction of oocyte maturation in the intact OCC incubated with FSH. Adenosine, ionophore, or FSH had no effect on oocyte maturation in denuded oocytes. Based on these results we conclude that the ionophores induced oocyte maturation by inhibition of FSH-dependent cAMP accumulation in the cumulus compartment, an effect that was probably calcium mediated. Since adenosine reversed the ionophore effects, we suggest that adenosine antagonizes the inhibitory effect of calcium on cAMP accumulation in cumulus cells and by this mechanism amplifies FSH inhibition of oocyte maturation.