期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 102, 期 7, 页码 2188-2198出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2017-00259
关键词
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资金
- Kurdistan Regional Government-Iraq scholarship funds (College of Veterinary Medicine, University of Duhok), a Commonwealth PhD scholarship
- Biotechnology and Biological Sciences Research Council case studentship
- BBSRC
- BBSRC [BBS/E/D/10002071, BBS/E/D/20221656] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/D/10002071, 1248216, BBS/E/D/20221656] Funding Source: researchfish
Context: Inadequate progesterone production from the corpus luteum is associated with pregnancy loss. Data available in model species suggest important roles of microRNAs (miRNAs) in luteal development and maintenance. Objective: To comprehensively investigate the involvement of miRNAs during the ovarian follicleluteal transition. Design: The effects of specific miRNAs on survival and steroid production by human luteinized granulosa cells (hLGCs) were tested using specific miRNA inhibitors. Candidate miRNAs were identified through microarray analyses of follicular and luteal tissues in a bovine model. Setting: An academic institution in the United Kingdom associated with a teaching hospital. hLGCs were obtained by standard transvaginal follicular-fluid aspiration from 35 women undergoing assisted conception. Intervention(s): Inhibition of candidate miRNAs in vitro. Main outcome measure(s): Levels of miRNAs, mRNAs, FOXO1 protein, apoptosis, and steroids were measured in tissues and/or cultured cells. Results: Two specific miRNA clusters, miR-183-96-182 and miR-212-132, were dramatically increased in luteal relative to follicular tissues. miR-96 and miR-132 were the most upregulated miRNAs within each cluster. Database analyses identified FOXO1 as a putative target of both these miRNAs. In cultured hLGCs, inhibition of miR-96 increased apoptosis and FOXO1 protein levels, and decreased progesterone production. These effectswere prevented by small interfering RNA-mediated downregulation of FOXO1. In bovine luteal cells, miR-96 inhibition also led to increases in apoptosis and FOXO1 protein levels. Conclusions: miR-96 targets FOXO1 to regulate luteal development through effects on cell survival and steroid production. The miR-183-96-182 cluster could provide a novel target for the manipulation of luteal function.
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