CELLULAR MESSENGERS AT FERTILIZATION IN MAMMALIAN EGGS

哺乳动物的卵子对受精的反应是戏剧性的 激活生理过程。离子通道打开，导致 膜电位发生变化。皮质颗粒经历 胞吐作用导致卵膜的修饰和 细胞外衣，并建立多精受精的障碍。 减数分裂，在第二个中期停止，恢复，卵子 为细胞分裂和进一步发展做准备。 在过去的几年里，已经获得了证据，基于 研究海胆和青蛙，卵子的激活可能是 由涉及鸟嘌呤核苷酸的一系列事件引发 结合蛋白、肌醇类脂代谢和释放 细胞内钙离子。这项研究的目的是 检查将精子-卵子接触耦合到 哺乳动物卵子发育的激活。特例 将重点研究皮质颗粒的起始 胞吐。在哺乳动物中，皮质颗粒的胞吐作用导致 在对卵细胞外衣的修饰中， 防止多精受精。胞吐作用也可能参与了 质膜阻止某些物种中的多精受精。 对胞吐作用的机制有了进一步的了解 这些研究将对其他研究多精受精的人有价值 预防机制。 这项研究的一个具体目的是在小鼠卵子中受精 是确定大脑皮层的时间和钙依赖 颗粒胞吐。另一个目标是检验一个假设 鸟嘌呤核苷酸结合蛋白负责激活。 细胞信使可能负责传导 激活信号包括三磷酸肌醇， 甘油二酯和钙；这项研究的其他目的是 确定这些物质在激活卵子中的作用。 在哺乳动物卵子中研究这些机制是很重要的。 受精的过程当然更类似于 出现在人类卵子中的那些。这项研究可能已经 对人类生殖及其基础研究的启示 研究可能会在人类生育问题上找到应用， 不孕不育、避孕和多精受精的发生。

The mammalian egg responds to fertilization with a dramatic activation of physiological processes. Ion channels open, causing the membrane potential to change. Cortical granules undergo exocytosis resulting in modification of the egg membrane and extracellular coats, and establishing a block to polyspermy. Meiosis, arrested at second metaphase, resumes, and the egg prepares for cell division and further development. Over the last several years, evidence has been obtained, based on studies of sea urchin and frog, that activation of the egg may be initiated by a sequence of events involving guanine nucleotide binding proteins, metabolism of inositol lipids, and release of intracellular calcium. The objective of this research is to examine the initial steps which couple sperm-egg contact to the activation of development in the mammalian egg. Particular emphasis will be on study of the initiation of cortical granule exocytosis. In mammals, exocytosis of cortical granules results in modification of the extracellular coats of the egg which prevents polyspermy. Exocytosis could also be involved in the plasma membrane block to polyspermy that occurs in some species. An understanding of the mechanism responsible for exocytosis gained from these studies will be valuable for others studying polyspermy preventing mechanisms. One specific aim of this study of fertilization in the mouse egg is to determine the timing and calcium-dependence of cortical granule exocytosis. Another aim is to test the hypothesis that a guanine nucleotide binding protein is responsible for activation. The cellular messengers that might be responsible for conducting the signal for activation include inositol triphosphate, diacylglycerol and calcium; the other aims of this study are to determine the role of these substances in activation of the egg. It is important to examine these mechanisms in a mammalian egg where the events of fertilization are certainly more similar to those occurring in the human egg. The research may have implications for study of human reproduction and this basic research may find applications to problems in human fertility, infertility, contraception, and occurrence of polyspermy.