Effects of aging on inositol 1,4,5-triphosphate-induced Ca2+ release in unfertilized mouse oocytes.

We previously demonstrated in the mouse oocyte that in vivo postovulatory aging significantly suppresses activity of the endoplasmic reticulum (ER) Ca 2+ -ATPase (Igarashi et al. 1997. Mol Reprod Dev 48:383-390). We undertook the present study to further examine the effects of oocyte aging on Ca 2+ release from the inositol 1,4,5-triphosphate (InsP 3 )-sensitive Ca 2+ channels of the ER membrane, because not only Ca 2+ reuptake, but also Ca 2+ release from the ER, substantially affect Ca 2+ oscillations in fertilized oocytes. A transient increase in cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) was induced by photolysis of caged InsP 3 microinjected into the cytoplasm in both fresh (14 hr post hCG) and aged (20 hr or 24 hr post hCG) oocytes, where the maximum rate of increase in [Ca 2+ ] i significantly decreased in the aged oocytes. Reduced ER Ca 2+ release in the aged oocyte may not be attributable to aging-related desensitization of the InsP 3 -sensitive Ca 2+ channels in the ER because concentrations of caged InsP 3 for half maximal [Ca 2+ ] i increase were identical for fresh and aged oocytes. The peak [Ca 2+ ] i response following administration of 5 μM thapsigargin, a specific ER Ca 2+ -ATPase inhibitor, was significantly reduced in the aged oocyte, suggesting reduction of the ER Ca 2 + stores. We conclude from these results that reduction of Ca 2+ release from the InsP 3 -sensitive Ca 2+ stores in the aged oocyte arises from depletion of the ER Ca 2+ stores with aging. These aging-related changes in Ca 2+ release and reuptake may account for alterations in Ca 2+ oscillations in aged fertilized oocytes.