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miRNA-7a2 通过 JNK 信号通路促进卵巢颗粒细胞中雌激素的合成，并受 FSH 调节。

MicroRNA-7a2 Contributes to Estrogen Synthesis and Is Modulated by FSH via the JNK Signaling Pathway in Ovarian Granulosa Cells.

机构信息

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Institute of Reproduction and Metabolism, Yangzhou University, Yangzhou 225009, China.

出版信息

Int J Mol Sci. 2022 Aug 2;23(15):8565. doi: 10.3390/ijms23158565.

DOI:10.3390/ijms23158565
PMID:35955699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9369042/
Abstract

MicroRNA-7a2 (miR-7a2) plays fundamental roles in the female reproductive axis, and estrogen is indispensable for maintaining ovary function. However, the interaction between miR-7a2 and ovarian function is unclear. The present study aimed to determine whether and how miR-7a2 functions in estrogen synthesis. Firstly, the results verified that miR-7a was highly expressed in ovarian granulosa cells. The knockout (KO) of miR-7a2 caused infertility and abnormal ovarian function in mice. Concomitantly, the expression and estrogen synthesis were significantly inhibited, which was validated in primary granulosa cells. The mice transplanted with miR-7a2 KO ovaries showed similar results; however, estrogen supplementation reversed infertility. In the in vitro experiment, follicle-stimulating hormone (FSH) significantly improved the expression of miR-7a and and the synthesis of estrogen. However, the miR-7a2 KO markedly reversed the function of FSH. Also, FSH upregulated miR-7a by activating the (c-Jun N-terminal kinase) JNK signaling pathway. In addition, Golgi apparatus protein 1 () was shown to be the target gene of miR-7a2. These findings indicated that miR-7a2 is essential for ovarian functions with respect to estrogen synthesis through the targeted inhibition of the expression of and then promoting expression; the physiological process was positively regulated by FSH via the JNK signaling pathway in granulosa cells.

摘要

微小 RNA-7a2 (miR-7a2) 在女性生殖轴中发挥着重要作用，而雌激素对于维持卵巢功能是不可或缺的。然而，miR-7a2 与卵巢功能之间的相互作用尚不清楚。本研究旨在确定 miR-7a2 是否以及如何在雌激素合成中发挥作用。首先，研究结果证实 miR-7a 在卵巢颗粒细胞中高表达。miR-7a2 的敲除（KO）导致小鼠不孕和卵巢功能异常。同时，在原代颗粒细胞中验证了表达和雌激素合成显著受到抑制。移植了 miR-7a2 KO 卵巢的小鼠也出现了类似的结果；然而，雌激素补充逆转了不孕。在体外实验中，卵泡刺激素 (FSH) 显著改善了 miR-7a 的表达和雌激素的合成。然而，miR-7a2 KO 显著逆转了 FSH 的功能。此外，FSH 通过激活（c-Jun N-末端激酶）JNK 信号通路上调 miR-7a。另外，高尔基器蛋白 1 () 被证明是 miR-7a2 的靶基因。这些发现表明，miR-7a2 通过靶向抑制的表达从而促进的表达，对于雌激素合成至关重要；该生理过程在颗粒细胞中通过 FSH 激活 JNK 信号通路得到正向调节。

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