Regulation of mitochondrial polarity in mouse and human oocytes: the influence of cumulus derived nitric oxide.

Whether exogenous factors influenced the level of mitochondrial polarity (DeltaPsim) in the subplasmalemmal cytoplasm of the oocyte was investigated with denuded and cumulus-enclosed human and mouse oocytes between the germinal vesicle and metaphase II stage. Co-culture of denuded oocytes with cumulus masses or primary cumulus cell cultures demonstrated a 'proximity' effect with respect to the detectable level of DeltaPsim in the oocyte. The specificity and reversibility of this effect on subplasmalemmal mitochondria were shown by repeated repositioning between cellular and acellular regions, which sequentially down- or up-regulated DeltaPsim. Experimental studies with a nitric oxide (NO) donor and inhibitor of NO synthase indicate that NO produced by cumulus cells has a regulatory influence on DeltaPsim in the subplasmalemmal cytoplasm of the corresponding oocyte. Culture of denuded and cumulus-enclosed (intact) oocytes in low and high oxygen atmospheres suggests that competition between oxygen and NO at the mitochondrial level may regulate the level of DeltaPsim and maintain mitochondria homeostasis in the pre-ovulatory oocyte, with a shift to higher polarity occurring after ovulation. The role of exogenous influences on oocyte DeltaPsim is discussed with respect to the regulation of developmental processes in the oocyte and early embryo.