Cooperative effects of 17β-estradiol and oocyte-derived paracrine factors on the transcriptome of mouse cumulus cells.

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Endocrinology Dec 2013; 154(12):4859-72.






Oocyte-derived paracrine factors (ODPFs) and estrogens are both essential for development and function of ovarian follicles in mammals. Cooperation of these two factors was assessed in vitro using intact cumulus-oocyte complexes (COCs), cumulus cells cultured after removal of oocytes (OOX cumulus cells), and OOX cumulus cells co-cultured with denuded oocytes, all in the presence or absence of 17β-estradiol (E2). Effects on the cumulus cell transcriptome were assessed by micro-array analysis. There was no significant difference between the cumulus cell transcriptomes of either OOX cumulus cells co-cultured with oocytes or intact COCs. 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 (GO) analysis revealed that both ODPFs and E2 strongly affected 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 biological processes related to phosphorylation-mediated signal transduction in cumulus cells, such as the signaling pathways of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF). Therefore, ODPFs and E2 cooperate to regulate the cumulus cell transcriptome and, in general, oocytes modulate the effects of estrogens on cumulus cell function. Endocrinology Dec 2013; 154(12):4859-72.