Regulation of Oocyte and Cumulus Cell Interactions by Intermedin/Adrenomedullin 2
Regulation of Oocyte and Cumulus Cell Interactions by Intermedin/Adrenomedullin 2
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DOI：
10.1074/jbc.m111.297358
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发表时间：
2011-12-16
影响因子：
4.8
通讯作者：
Hsu, Sheau Yu Teddy
中科院分区：
文献类型：
--
作者：
Chang, Chia Lin;Wang, Hsin-Shih;Hsu, Sheau Yu Teddy
卵巢卵泡发生已被研究为激素调节发育和分化、细胞死亡和细胞间通讯的模型。除了来自垂体的促性腺激素和卵泡旁分泌因子外，卵母细胞分泌因子已被证明在卵泡细胞功能的调节中起关键作用。除了充分表征的BMP家族蛋白，包括GDF 9和BMP 15，已知卵母细胞分泌卵母细胞分泌因子，其对于调节卵丘细胞存活和维持卵丘细胞封闭的卵母细胞复合物（COCs）的三级结构是重要的。基于基因组筛选和体外培养的COCs的研究，我们发现，intermedin（IMD）/肾上腺髓质素2（ADM 2）是一种新的卵母细胞衍生的配体重要的COCs的功能，部分通过抑制卵丘细胞凋亡的细胞相互作用的调节。因此，我们发现在体内生长的大鼠卵巢中抑制IMD/ADM 2信号传导导致卵母细胞闭锁和卵泡细胞中细胞周期进程异常。总之，我们的研究表明，哺乳动物卵母细胞部署G蛋白偶联受体配体，以协调卵母细胞和卵丘细胞的正常相互作用，并提供了一个更好的理解如何维持COC的三级结构作为卵泡经历指数生长在卵泡发育的后期阶段。
Ovarian folliculogenesis has been studied as a model of hormonal regulation of development and differentiation, cell death, and cell-cell communication. In addition to gonadotropins from the pituitary and follicular paracrine factors, oocyte secreted factors have been shown to play critical roles in the regulation of follicular cell functions. Except for the well characterized BMP family proteins, including GDF9 and BMP15, oocytes are known to secrete oocyte secreted factors that are important for the regulation of cumulus cell survival and the maintenance of tertiary structure of cumulus cell-enclosed oocyte complexes (COCs). Based on genomic screening and studies of COCs cultured in vitro, we showed that intermedin (IMD)/adrenomedullin 2 (ADM2) is a novel oocyte-derived ligand important for the regulation of cell interactions in COCs that functions, in part, by suppressing cumulus cell apoptosis. Consistently, we showed that suppression of IMD/ADM2 signaling in growing rat ovaries in vivo leads to oocyte atresia and aberrant cell cycle progression in follicular cells. Together, our studies indicated that mammalian oocytes deploy a G protein-coupled receptor ligand to coordinate normal interactions of oocytes and cumulus cells and provided a better understanding of how the tertiary structure of a COC is maintained as follicles undergo exponential growth during the late stages of folliculogenesis.