Gap-junctional communication in mouse cumulus-oocyte complexes: implications for the mechanism of meiotic maturation

The mechanisms underlying the hormonal stimulation of meiotic maturation are not understood. The most prevalent hypothesis is that hormone-induced maturation is stimulated by an increase in the intracellular messengers, cAMP or Ca2+. This study investigated whether Ca2+ transients in somatic cells can lead to Ca2+ transients in the oocyte, and whether hormones that stimulate meiotic maturation of mouse oocytes in vitro and in vivo stimulate an increase in intracellular Ca2+. Of a range of potential agonists of Ca2+ release, ATP and UTP were the only agents that stimulated Ca2+ release in cumulus cells. ATP-induced Ca2+ release is from intracellular stores, as the response is not blocked by chelation of extracellular Ca2+, but is inhibited by the Ca2+-ATPase inhibitor, thapsigargin. ATP and UTP are equipotent, consistent with the receptor being of the P2Y2 type. Confocal microscopy was used to show that ATP-induced Ca2+ release in cumulus cells leads to a Ca2+ increase in the oocyte. Inhibition of gap-junctional communication using carbenoxolone, as assayed by dye transfer, inhibited the diffusion of the Ca2+ signal from the cumulus cells to the oocyte. Thus, provided that a Ca2+ signal is generated in the somatic cells in response to maturation-inducing hormones, it is feasible that a Ca2+ transient is generated in the oocyte. However, FSH and EGF, both of which stimulate maturation in vitro, have no effect on Ca2+ in cumulus--oocyte complexes. Furthermore, LH, which leads to meiotic maturation in vivo, did not stimulate Ca2+ release in acutely isolated granulosa cells from preovulatory mouse follicles. These studies indicate that ATP may play a role in modulating ovarian function and that diffusion of Ca2+ signals through gap junctions may provide a means of communication between the somatic and germ cells of the ovarian follicle. However, our data are not consistent with a role for Ca2+-mediated communication in hormone-mediated induction of meiosis in mice.

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