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8 May 2017 MicroRNA-21 plays a pivotal role in the oocyte-secreted factor-induced suppression of cumulus cell apoptosis
Xiao Han, Rui Xue, Hong-Jie Yuan, Tian-Yang Wang, Juan Lin, Jie Zhang, Bo Liang, Jing-He Tan
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Abstract

It is known that oocytes and cumulus cells (CCs) are more resistant to apoptosis than other compartments of the antral follicle. However, although oocyte-secreted factors (OSFs) have been found to be involved in suppressing bovine CC apoptosis, little is known about the intracellular mechanisms by which OSFs render CCs resistant to apoptosis. Here, we show that coculture with mouse or pig cumulus-denuded oocytes, culture with recombinant mouse growth differentiation factor-9 (GDF-9), or culture in pig oocyte-conditioned medium (POCM) significantly inhibited CC apoptosis of mouse oocytectomized cumulus oophorus complexes (OOXs). The POCM contained both GDF-9 and bone morphogenetic protein-15, and their levels remained constant during culture of OOXs. The level of microRNA-21 (miR-21) was significantly lower in OOXs than in COCs after culture in a simplified α-MEM medium, but increased significantly when OOXs were cultured with GDF-9 or in POCM. The level of miR-21 in OSF-treated CCs was correlated with that of Dicer1 but not that of Drosha mRNA. Inhibiting activin receptor-like kinase 5 or SMAD3 completely abolished the beneficial effects of GDF-9 or POCM on CC apoptosis and miR-21 levels. Up- and downregulating miR-21 expression significantly reduced and increased CC apoptosis, respectively. The OSF-upregulated miR-21 expression suppressed CC apoptosis with activation of the PI3K/Akt signaling. In conclusion, miR-21 plays a pivotal role in the OSF suppression of CC apoptosis. OSFs upregulated miR-21 expression through the TGF-β superfamily signaling, which worked through DICER. MicroRNA-21 prevented apoptosis via the PI3K/Akt signaling.

Summary Sentence

MicroRNA-21 plays a pivotal role in the oocyte-secreted factor suppression of cumulus cell apoptosis to explore the intracellular mechanisms by which oocyte-secreted factors suppress cumulus cell apoptosis.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Xiao Han, Rui Xue, Hong-Jie Yuan, Tian-Yang Wang, Juan Lin, Jie Zhang, Bo Liang, and Jing-He Tan "MicroRNA-21 plays a pivotal role in the oocyte-secreted factor-induced suppression of cumulus cell apoptosis," Biology of Reproduction 96(6), 1167-1180, (8 May 2017). https://doi.org/10.1093/biolre/iox044
Received: 24 April 2017; Accepted: 8 May 2017; Published: 8 May 2017
JOURNAL ARTICLE
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