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10 July 2013 Oocyte-Secreted Growth Differentiation Factor 9 Inhibits BCL-2-Interacting Mediator of Cell Death-Extra Long Expression in Porcine Cumulus Cell
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Abstract

Oocyte-secreted factors (OSFs) maintain the low incidence of cumulus cell apoptosis. In this report, we described that the presence of oocytes suppressed the expression of proapoptotic protein BCL-2-interacting mediator of cell death-extra long (BIMEL) in porcine cumulus cells. Atretic (terminal deoxynu cleotidyl transferase dUTP nick end labeling-positive) cumulus cells strongly expressed BIMEL protein. The healthy cumulus- oocyte complex exhibited a low BIMEL expression in cumulus cell while the removal of oocyte led to an about 2.5-fold (P < 0.5) increased expression in oocytectomized complex (OOX). Coculturing OOXs with denuded oocytes decreased BIMEL expression to the normal level. The similar expression pattern could also be achieved in OOXs treated with exogenous recombinant mouse growth differentiation factor 9 (GDF9), a well-characterized OSF. This inhibitory action of GDF9 was prevented by the addition of a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Luciferase assay further demonstrated that BIM gene expression was forkhead box O3a (FOXO3a)-dependent because mutation of FOXO3a-binding site on the BIM promoter inhibited luciferase activities. Moreover, the activity of BIM promoter encompassing the FOXO3a-binding site could be regulated by GDF9. Additionally, we found that GDF9 elevated the levels of phosphorylated AKT and FOXO3a, and this process was independent of the SMAD signal pathway. Taken together, we concluded that OSFs, particularly GDF9, maintained the low level of BIMEL expression in cumulus cell through activation of the PI3K/FOXO3a pathway.

Xian-Long Wang, Kun Wang, Shuan Zhao, Yi Wu, Hui Gao, and Shen-Ming Zeng "Oocyte-Secreted Growth Differentiation Factor 9 Inhibits BCL-2-Interacting Mediator of Cell Death-Extra Long Expression in Porcine Cumulus Cell," Biology of Reproduction 89(3), (10 July 2013). https://doi.org/10.1095/biolreprod.113.108365
Received: 31 January 2013; Accepted: 1 June 2013; Published: 10 July 2013
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