Cooperative Effects of 17β-Estradiol and Oocyte-Derived Paracrine Factors on the Transcriptome of Mouse Cumulus Cells
Cooperative Effects of 17β-Estradiol and Oocyte-Derived Paracrine Factors on the Transcriptome of Mouse Cumulus Cells
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DOI：
10.1210/en.2013-1536
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发表时间：
2013-12-01
期刊：
影响因子：
4.8
通讯作者：
Sugiura, Koji
中科院分区：
文献类型：
--
作者：
Emori, Chihiro;Wigglesworth, Karen;Sugiura, Koji
卵母细胞衍生的旁分泌因子(ODPF)和雌激素对哺乳动物卵泡的发育和功能都是必不可少的。使用完整的卵丘-卵母细胞复合体、去除卵母细胞后培养的卵丘细胞[卵母细胞摘除(OOX)卵丘细胞]以及与裸卵母细胞共同培养的卵丘细胞，在体外评估这两种因素的协同作用，所有这些都在有或没有17β-雌二醇(E_2)的情况下。通过基因芯片分析，评估对卵丘细胞转录组的影响。与卵母细胞共培养的OOX卵丘细胞和完整的卵丘-卵母细胞复合体的卵丘细胞转录产物无显著差异。因此，卵母细胞对卵丘细胞转录组的调控主要是通过ODPF介导的，而不是通过卵母细胞和卵丘细胞之间的缝隙连接通讯来实现的。基因本体论分析表明，ODPF和E2都强烈影响卵丘细胞中与细胞增殖相关的生物学过程。雌二醇对ODPF调节的生物学过程的影响有限。然而，与之形成鲜明对比的是，ODPF显著影响了卵丘细胞中受E2调控的生物学过程。例如，只有在ODPFs存在的情况下，E2才能显著促进卵丘细胞中与磷酸化介导的信号转导相关的生物学过程，如表皮生长因子、血管内皮生长因子和血小板衍生生长因子的信号通路。因此，ODPF和E2共同调节卵丘细胞转录组，总体上，卵母细胞调节雌激素对卵丘细胞功能的影响。
Oocyte-derived paracrine factors (ODPFs) and estrogens are both essential for the development and function of ovarian follicles in mammals. Cooperation of these two factors was assessed in vitro using intact cumulus-oocyte complexes, cumulus cells cultured after the removal of oocytes [oocytectomized (OOX) cumulus cells], and OOX cumulus cells cocultured with denuded oocytes, all in the presence or absence of 17 beta-estradiol (E2). Effects on the cumulus cell transcriptome were assessed by microarray analysis. There was no significant difference between the cumulus cell transcriptomes of either OOX cumulus cells cocultured with oocytes or intact cumulus-oocyte complexes. Therefore, oocyte-mediated regulation of the cumulus cell transcriptome is mediated primarily by ODPFs and not by gap junctional communication between oocytes and cumulus cells. Gene ontology analysis revealed that both ODPFs and E2 strongly affected the biological processes associated with cell proliferation in cumulus cells. E2 had limited effects on ODPF-regulated biological processes. However, in sharp contrast, ODPFs significantly affected biological processes regulated by E2 in cumulus cells. For example, only in the presence of ODPFs did E2 significantly promote the biological processes related to phosphorylation-mediated signal transduction in cumulus cells, such as the signaling pathways of epidermal growth factor, vascular endothelial growth factor, and platelet-derived growth factor. Therefore, ODPFs and E2 cooperate to regulate the cumulus cell transcriptome and, in general, oocytes modulate the effects of estrogens on cumulus cell function.