国际生殖健康/计划生育杂志

国际生殖健康/计划生育 ›› 2019, Vol. 38 ›› Issue (1): 43-47.

• 论著 • 上一篇    下一篇

早期妊娠丢失蜕膜组织中与血管重塑相关的miRNAs表达谱分析

俞田田，洪丽华   

  1. 200030上海交通大学附属国际和平妇幼保健院（俞田田）；浙江大学医学院附属妇产科医院（洪丽华）
  • 收稿日期:2018-08-30 修回日期:2018-10-18 出版日期:2019-01-15 发布日期:2019-01-15
  • 通讯作者: 洪丽华，E-mail：honglh1008@163.com E-mail:honglh@zju.edu.cn
  • 基金资助:
    浙江省医药卫生科技项目（201718390）

Expression Profile of MiRNAs Associated with Vascular Remodeling in Decidual Tissue of Early Pregnancy

YU Tian-tian, HONG Li-hua   

  1. The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China（YU Tian-tian）；Women′s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, Chinａ（HONG Li-huａ）
  • Received:2018-08-30 Revised:2018-10-18 Published:2019-01-15 Online:2019-01-15
  • Contact: HONG Li-hua, E-maiｌ： honglh1008@163.com E-mail:honglh@zju.edu.cn

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摘要： 目的：通过对子宫内膜蜕膜化中与血管重塑相关的miRNAs表达谱的芯片筛查及相关靶基因预测，为早期妊娠丢失的发病机制研究奠定基础。方法：利用miRNA array芯片检测早期妊娠丢失患者蜕膜组织中的差异表达miRNAs，确定与血管重塑相关的miRNAs表达谱，进而应用miRWalk2.0数据库通过生物信息学方法预测差异表达miRNAs的相关靶基因，最后应用DAVID数据库对相关靶基因进行功能富集分析（GO-analysis）及靶基因信号转导通路富集分析（KEGG Pathway analysis）。结果：早期妊娠丢失患者蜕膜组织中差异表达的miRNAs共70条，上调表达miRNAs 32条，下调表达miRNAs 38条。其中差异倍数最高（≥2.0）的2个上调miRNA为miR-125a-5p和miR-29c-3p，预测相关靶基因为血管内皮生长因子A（VEGFA）。靶基因集合功能富集于正调控RNA代谢过程、血管发育、脉管系统发育、正调控内皮细胞增殖、缺氧反应、血管生成等分子过程；KEGG通路分析涉及哺乳动物雷帕霉素靶蛋白（mTOR）信号通路、丝裂原活化蛋白激酶（MAPK）等信号通路。结论：miR-125a-5p和miR-29c-3p在早期妊娠丢失患者蜕膜组织中上调表达，可能通过对靶基因VEGFA的调控，影响子宫内膜蜕膜化血管重塑的过程，参与流产发生。

关键词: 流产, 自然, 妊娠初期, 微RNAs, 计算生物学, 血管内皮生长因子A, 血管重塑

Abstract: Objective：To explore the expression profile of miRNAs related to vascular remodeling of endometrium, and to predict the target genes, as a pioneer research of the pathogenesis of early pregnancy loss (EPL). Methods: The differentially expressed miRNAs in the decidual tissues of EPL were tested using the miRNA microarray, and the expression profile of miRNAs related to vascular remodeling was determined. The target genes of those differentially expressed miRNAs were screened using miRWalk2.0 database. The bioinformatics analysis of these target genes was performed by Gene Ontology analysis (GO-analysis) and Kyoto Encyclopedia of Genes and Genomes Pathway analysis (KEGG Pathway analysis). Results: There were 70 differentially expressed miRNAs in the deciduas tissues of EPL, including 32 up-regulated and 38 down-regulated miRNAs. MiR-125a-5p and miR-29c-3p were two miRNAs with the highest difference times (Ratio＞2.0) in those up-regulated miRNAs, and the predicted target gene was VEGFA. The function of target gene set was mainly located in the positive regulation of RNA metabolism, vascular development, endothelial cell proliferation and hypoxia and angiogenesis. KEGG pathway analysis demonstrated that the gene set was mostly located in mTOR signaling pathway and MAPK signaling pathway. Conclusions: The up-regulated expressions of miR-125a-5p and miR-29c-3p may affect the vascular remodeling in endometrial decidualization by regulating the VEGFA expression, suggesting that miR-125a-5p and miR-29c-3p participate in the pathogenesis of EPL.

Key words: Abortion, spontaneous, Pregnancy trimester, first, MicroRNAs, Computational biology, Vascular endothelial growth factor A, Vascular remodeling