遗传 ›› 2020, Vol. 42 ›› Issue (10): 1004-1016.doi: 10.16288/j.yczz.20-144

• 研究报告 • 上一篇    下一篇

早期停育胚胎的滋养层细胞相关基因与特征分析

张悦1, 冯颖2, 马芳1,3()   

  1. 1. 四川大学华西第二医院教育部“妇儿疾病与出生缺陷”重点实验室,成都 610041;
    2. 四川大学华西基础医学与法医学院,成都 610041
    3. 四川大学华西第二医院妇产科,成都 610041
  • 收稿日期:2020-08-08 修回日期:2020-10-02 出版日期:2020-10-20 发布日期:2020-10-15
  • 通讯作者: 马芳 E-mail:mafangmed@126.com
  • 作者简介:张悦,在读硕士研究生,专业方向:母婴医学。E-mail: zhangyue@stu.scu.edu.cn
  • 基金资助:
    国家自然科学基金项目编号(31771662);国家科技重大专项资助编号(2018YFC1002803-3)

Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation

Zhang Yue1, Feng Ying2, Ma Fang1,3()   

  1. 1. Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
    2. West China School of Basic Medical Sciences & Forensic Medicine, Chengdu 610041, China;
    3. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China
  • Received:2020-08-08 Revised:2020-10-02 Online:2020-10-20 Published:2020-10-15
  • Contact: Ma Fang E-mail:mafangmed@126.com
  • Supported by:
    Supported by the National Nature Science Foundation of China No(31771662);the National Science and Technology Major Project No(2018YFC1002803-3)

摘要:

滋养层细胞对维持正常胚胎植入、生长发育有重要作用。研究停育胚胎的滋养层细胞的基因表达差异有助于了解胚胎发育停止或不良妊娠结局的发生发展机制。本研究通过对26例正常妊娠、胚胎停育妇女的绒毛组织进行全转录组测序和初步生物信息学分析,发现胚胎停育组存在436个差异基因,其中406个mRNA为显著上调基因,32个mRNA为显著下调基因。基因富集分析显示这些基因显著富集于免疫相关功能、细胞间黏附等方面,如淋巴细胞激活、髓系细胞激活、细胞外基质及胶原连接等,其潜在调控通路富集到补体及凝血级联反应和细胞外基质降解等条目。此外,本研究利用WGCNA共表达分析得到和差异基因存在共表达关系的lncRNA。根据模块功能不同,绘制了两个网络图,可得4个关键基因,分别为VSIG4、C1QC、CD36SPP1。本研究得到的这些差异基因可作为对胚胎停育具有潜在影响的关键分子,所富集到的条目可为深入了解胚胎发育停止或不良妊娠结局的病因及机制提供理论依据及方向。

关键词: 滋养层细胞, RNA测序, 富集分析, 基因特征

Abstract:

Trophoblast cells play essential roles in the maintenance of normal embryo implantation, growth and development. The study of abnormal gene changes in trophoblastic cells from arrested embryos is helpful to understand the developmental mechanism of embryo developmental cessation or adverse pregnancy outcomes. In this study, we sequenced and analyzed the transcriptomes of the villi from ten women who have undergone abortion with either normal pregnancy or embryo development cessation. We found that there were 436 differentially expressed genes, of which 406 mRNA were significantly up-regulated and 32 mRNA were significantly down-regulated. Gene enrichment analysis showed that these genes were significantly enriched in immune-related functions and intercellular adhesion, such as lymphocyte activation, myeloid cell activation, extracellular matrix and collagen junction. And their potential regulatory pathways were enriched in terms of complement and coagulation cascade, extracellular matrix degradation. In addition, in this study the co-expression analysis of WGCNA was used to obtain the lncRNA with co-expression relationship with the differential genes. According to the different functions of the modules, two network diagrams were drawn, and four key genes were obtained, namely VSIG4, C1QC, CD36 and SPP1. These differential genes obtained in this study can be used as key molecules with potential effects on embryo development cessation. The enriched entries can provide a theoretical basis and new direction for further understanding of the etiology and mechanism of embryo development cessation or adverse pregnancy outcomes.

Key words: trophoblast, RNA-seq, enrichment analysis, genetic traits