期刊
DOMESTIC ANIMAL ENDOCRINOLOGY
卷 74, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.domaniend.2020.106509
关键词
Pig; Follicular atresia; miR-146b; CYP19A1; Granulosa cell apoptosis
资金
- National Natural Science Foundation of China, China [31630072, 31572373]
- Qing Lan Project
miR-146b is a novel epigenetic factor that regulates GC functions, follicular development, and female reproduction in pigs by targeting CYP19A1 for E2 synthesis signaling.
MicroRNAs (miRNAs) are 21- to 24-nucleotide long small noncoding RNAs, which play an important role in follicular atresia and granulosa cell (GC) apoptosis in the mammalian ovary. Here, we report that miR-146b, a conserved and ovary-enriched miRNA, modulates estradiol (E2) secretion, GC apoptosis, and follicular atresia in pigs. Genome-wide analysis and quantitative real-time PCR revealed that miR-146b was significantly upregulated during follicular atresia, and fluorescence-activated cell sorting showed that miR-146b functioned as a proapoptotic factor to induce GC apoptosis. MicroRNA-mRNA network analysis and luciferase reporter assays showed that CYP19A1, the pivotal enzyme for E2 synthesis signaling, was directly targeted by miR-146b. Furthermore, miR-146b interacted with the 3'untranslated region of CYP19A1 to prevent translation, thereby regulating CYP19A1-mediated E2 secretion and GC apoptosis. However, miR-146b was not regulated by the transcription factor SMAD4 or oxidative stress, both of which are critical regulators of CYP19A1. We, thus, conclude that miR-146b is a novel epigenetic factor regulating GC functions, follicular development, and female reproduction. (C) 2020 Elsevier Inc. All rights reserved.
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