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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Timely Interaction Between Prostaglandin And Chemokine Signaling Is A Prerequisite For Successful Fertilization
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Timely Interaction Between Prostaglandin And Chemokine Signaling Is A Prerequisite For Successful Fertilization

机译：前列腺素与趋化因子信号之间的及时相互作用是成功受精的前提

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摘要

Timely interaction between the egg and sperm is required for successful fertilization; however, little is known about the signaling therein. Prostaglandin (PG) E receptor EP2-deficient (Ptger2~(-/-)) female mice exhibit a severe fertilization defect. We investigated the molecular events leading to this failure. We found increased gene expression for chemokines, such as Cc/2, Ccl7, and Cc/9, in Ptger2~(-/-) cumulus cells (the somatic cells surrounding the egg) compared with wild-type cells. Furthermore, under physiological conditions, cumulus-derived chemokine signaling was found to have a dual action; CCL7 facilitates sperm migration to the cumulus-egg complex and integrin-mediated cumulus extracellular matrix (ECM) assembly to protect eggs. However, in the absence of PGE2-EP2 signaling, chronic CCL7 signaling results in excessive integrin engagement to the ECM, making the cumulus ECM resistant to sperm hyaluronidase, thereby preventing sperm penetration. Our findings indicate that PGE2-EP2 signaling negatively regulates the autocrine action of chemokines and prevents excessive cumulus ECM assembly. This interaction between PG and chemokine signaling is required for successful fertilization.
机译：成功受精需要卵与精子之间及时相互作用。然而，关于其中的信令知之甚少。缺乏前列腺素（PG）E受体EP2的雌性小鼠（Ptger2〜（-/-））表现出严重的受精缺陷。我们调查了导致这种失败的分子事件。我们发现与野生型细胞相比，Ptger2〜（-/-）卵丘细胞（卵周围的体细胞）中趋化因子（例如Cc / 2，Ccl7和Cc / 9）的基因表达增加。此外，在生理条件下，发现积云趋化因子信号传导具有双重作用。 CCL7促进精子迁移到卵-卵复合体和整联蛋白介导的卵丘细胞外基质（ECM）组装，以保护卵子。但是，在没有PGE2-EP2信号传导的情况下，慢性CCL7信号传导会导致整联蛋白过度参与ECM，从而使积云ECM对精子透明质酸酶产生抵抗力，从而阻止了精子的渗透。我们的发现表明，PGE2-EP2信号负调节趋化因子的自分泌作用，并防止过多的积云ECM组装。 PG和趋化因子信号传导之间的这种相互作用是成功受精所必需的。

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