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Since our previous studies indicate that microRNA-181a (miR-181a) expression is increased in GCs undergoing apoptosis, the present study was designed to define the relationship between exposure to oxidative stressors in GCs and changes in miR-181a expression and function. To achieve this, we employed an H2O2-induced in vitro model and a 3-nitropropionic acid-induced in vivo model of ovarian oxidative stress. We demonstrated that in vitro miR-181a overexpression promoted GC apoptosis in a dose-dependent manner; sphingosine-1-phosphate (S1P) significantly reversed both H2O2-induced and miR-181a-induced apoptosis in GCs. Moreover, we identified sphingosine-1-phosphate receptor 1 (S1PR1), a critical receptor of S1P, as a novel target of miR-181a in GCs. MicroRNA-181a induced GC apoptosis by repressing S1PR1 expression in vitro. Importantly, increased miR-181a expression and decreased S1PR1 expression were detected in the in vivo ovarian oxidative stress model by Western blot analysis and immunohistochemistry. Furthermore, we found similar expression patterns of miR-181a and S1PR1 in GCs from patients with premature ovarian insufficiency. In conclusion, our results suggest that miR-181a directly suppresses expression of S1PR1, which has critical roles in mediating oxidative stress-induced GC apoptosis both in vitro and in vivo.<\/jats:p>","DOI":"10.1093\/biolre\/ioz135","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T03:00:24Z","timestamp":1564455624000},"page":"975-985","source":"Crossref","is-referenced-by-count":24,"title":["MicroRNA-181a promotes follicular granulosa cell apoptosis via sphingosine-1-phosphate receptor 1 expression downregulation\u2020"],"prefix":"10.1093","volume":"101","author":[{"given":"Chunxue","family":"Zhang","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingtao","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The 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