miR-183-5p regulates uterine receptivity and enhances embryo implantation
miR-183-5p regulates uterine receptivity and enhances embryo implantation
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miR-183-5p调节子宫容受性并增强胚胎着床
DOI：
10.1530/jme-19-0184
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发表时间：
2020-01-01
影响因子：
3.5
通讯作者：
Sheng, Jian-Zhong
中科院分区：
文献类型：
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作者：
Akbar, Rubab;Ullah, Kamran;Sheng, Jian-Zhong
容受性子宫内膜是胚胎着床成功的先决条件，因此，子宫内膜容受性差是导致着床失败的主要原因。MiRNAs通过转录后修饰对子宫内膜容受性和胚胎着床起着重要的表观遗传调节作用。然而，许多miRNAs的作用机制尚不清楚。在本研究中，我们研究了miR-183家族，包括三个miRNAs(miR-183-5p、miR-182-5p和miR-96-5p)在子宫内膜容受性和胚胎着床中的作用。MiR-183家族显示雌激素依赖的子宫内膜Ishikawa(IK)细胞表达上调。MiR-183家族在IK细胞的迁移和增殖中也起着积极的作用。此外，JAR球体贴壁实验表明，经miR-183-5P和miR-182-5P抑制剂处理的IK细胞贴壁率显著降低，经miR-183-5P和miR-96-5P-MIMIC处理后贴壁率显著增加。下游分析表明，连环蛋白α2(CTNNA2)是miR-183-5p的潜在靶基因，荧光素酶报告基因分析证实了这一点。小鼠体内妊娠模型显示，抑制miR-183-5p显著降低胚胎着床率，并增加CTNNA2的表达。MiR-183-5p下调子宫内膜细胞CTNNA2的表达可能在介导雌激素对子宫内膜容受性的影响中起重要作用。总之，miR-183-5p和CTNNA2基因可能是子宫内膜容受性的潜在生物标志物，并可能成为胚胎着床成功的诊断和治疗靶点。
Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.