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- Title
GDNF-Induced Downregulation of miR-145-5p Enhances Human Oocyte Maturation and Cumulus Cell Viability.
- Authors
Cui, Long; Fang, Li; Mao, Xiaodan; Chang, Hsun-Ming; Leung, Peter C K; Ye, Yinghui
- Abstract
<bold>Context: </bold>Although glial cell line-derived neurotrophic factor (GDNF) and microRNAs (miRNAs) have been shown to regulate mammalian oocyte maturation, little is known about their effects on human oocyte maturation and the underlying molecular mechanisms.<bold>Objectives: </bold>To examine the effects of GDNF on both nuclear and cytoplasmic maturation in cultured immature human oocytes and to investigate the involvement of miRNAs in GDNF-induced oocyte maturation.<bold>Design: </bold>A total of 200 human immature oocytes were used to evaluate the effects of GDNF on oocyte maturation. The involvement of miRNAs in GDNF-induced oocyte maturation was identified by comparing the miRNA expression profiles of cumulus cells (CCs) either with or without GDNF stimulation.<bold>Setting: </bold>An in vitro fertilization center at the Women's Hospital, Zhejiang University School of Medicine.<bold>Methods: </bold>Agilent human miRNA (8*60K) arrays were used to examine the miRNA expression patterns of human CCs either with or without GDNF stimulation. miR-145-5p inhibitor and mimic transfections were performed to study downstream gene expression in human CCs.<bold>Results: </bold>During the in vitro maturation process, GDNF significantly increased the percentage of metaphase II-stage oocytes and downregulated the expression of miR-145-5p in cultured human CCs. Expression of miR-145-5p in CCs is negatively correlated with oocyte maturation. miR-145-5p mimic significantly decreased the expression of GDNF family receptor-α1, ret proto-oncogene, and epidermal growth factor receptor, whereas miR-145-5p inhibitor reversed these effects. GDNF treatment inhibited cell apoptosis in cultured CCs, and this suppressive effect was reversed by transfection with the miR-145-5p mimic.<bold>Conclusion: </bold>Downregulation of miR-145-5p may contribute to GDNF-induced enhancement of oocyte maturation and of cell viability against cell apoptosis.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2018, pN.PAG
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2017-02742