MicroRNA-181a promotes follicular granulosa cell apoptosis via sphingosine-1-phosphate receptor 1 expression downregulation

Oxidative stress induces granulosa cell (GC) apoptosis and subsequent follicular atresia. 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 str...

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Bibliographic Details
Published in:Biology of reproduction 2019-11, Vol.101 (5), p.975-985
Main Authors: Zhang, Chunxue, Shen, Jingtao, Kong, Shuangbo, Zhang, Mei, Zhang, Qun, Zhou, Jidong, Zhen, Xin, Kang, Nannan, Jiang, Yue, Ding, Lijun, Sun, Haixiang, Yan, Guijun
Format: Article
Language:English
Subjects:
Apoptosis
Genetic aspects
granulosa cell
Immunohistochemistry
MicroRNA
microRNA-181a
MicroRNAs
Novels
Oxidative stress
Phosphates
Physiological aspects
RESEARCH ARTICLE
S1PR1
Somatic cells
Sphingosine
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Summary:Oxidative stress induces granulosa cell (GC) apoptosis and subsequent follicular atresia. 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. Summary sentence MicroRNA-181a directly suppresses expression of S1PR1, which has critical roles in mediating oxidative stress-induced GC apoptosis both in vitro and in vivo.
ISSN:0006-3363
1529-7268
DOI:10.1093/biolre/ioz135