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复发性流产患者胎盘绒毛中miR-486-3p和miR-3074-5p的异常表达及小鼠妊娠早期子宫中这些微小RNA的表达

Aberrant Placental Villus Expression of miR-486-3p and miR-3074-5p in Recurrent Miscarriage Patients and Uterine Expression of These MicroRNAs during Early Pregnancy in Mice.

作者信息

Gu Yan, Zhang Xuan, Yang Qian, Wang Jianmei, He Yaping, Sun Zhaogui, Zhang Huiqin, Wang Jian

机构信息

Shanghai Medical School, Fudan University, Shanghai, China.

出版信息

Gynecol Obstet Invest. 2015 Aug 5. doi: 10.1159/000435879.

Abstract

MicroRNAs (miRNAs) are critical regulators of gene expression; they have emerged as new players in the pathophysiology of reproductive disorders such as preeclampsia and recurrent miscarriage (RM). In this study, miRNA expression profiles were determined by deep sequencing analysis in placental villi obtained from women with RM and with gestational age-matched normal pregnancy (NP). A total of 69 miRNAs were found to be aberrantly expressed in RM. Five of these human (Homo sapiens) miRNAs (hsa-miRNAs), including hsa-miR-3074-5p, -486-3p, -1269b, -6765-3p and -144-3p, were validated by qRT-PCR in 12 RM and 10 NP placental villi. Hsa-miR-3074-5p expression was significantly higher, while hsa-miR-486-3p expression was significantly lower, in RM compared to NP. Subsequently, the expression of mouse (Mus musculus) miR-486-3p (mmu-miR-486-3p) and mmu-miR-3074-5p, which are identical to hsa-miR-486-3p and hsa-miR-3074-5p, respectively, were examined by qRT-PCR in the uterus during early pregnancy. Mmu-miR-486-3p expression was significantly increased during the peri-implantation period, and the levels were significantly higher at implantation than at non-implantation sites. In contrast, the expression of mmu-miR-3074-5p was markedly decreased at implantation compared to non-implantation sites. These data suggest that miR-486-3p and miR-3074-5p may be involved in embryo implantation and that their aberrant expression is associated with RM. Larger studies are warranted to follow up this pilot study. © 2015 S. Karger AG, Basel.

摘要

微小RNA(miRNA)是基因表达的关键调节因子;它们已成为诸如子痫前期和复发性流产(RM)等生殖系统疾病病理生理学中的新因素。在本研究中,通过深度测序分析确定了从患有RM的女性以及与妊娠年龄匹配的正常妊娠(NP)女性获取的胎盘绒毛中的miRNA表达谱。共发现69种miRNA在RM中异常表达。其中5种人类(智人)miRNA(hsa-miRNA),包括hsa-miR-3074-5p、-486-3p、-1269b、-6765-3p和-144-3p,在12例RM和10例NP胎盘绒毛中通过qRT-PCR进行了验证。与NP相比,RM中hsa-miR-3074-5p表达显著升高,而hsa-miR-486-3p表达显著降低。随后,通过qRT-PCR检测了在妊娠早期子宫中与hsa-miR-486-3p和hsa-miR-3074-5p分别相同的小鼠(小家鼠)miR-486-3p(mmu-miR-486-3p)和mmu-miR-3074-5p的表达。mmu-miR-486-3p在植入前期表达显著增加,且植入部位的水平显著高于未植入部位。相反,与未植入部位相比,mmu-miR-3074-5p在植入时的表达明显降低。这些数据表明,miR-486-3p和miR-3074-5p可能参与胚胎植入,且它们的异常表达与RM有关。需要更大规模的研究来跟进这项初步研究。© 2015 S. Karger AG,巴塞尔。

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