Chen Yihong, Hu Jifen
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China (mainland).
Med Sci Monit. 2020 Oct 8;26:e927537. doi: 10.12659/MSM.927537.
BACKGROUND The molecular mechanism of recurrent spontaneous abortion is unclear. It has been suggested that dysregulated genes participate in the pathogenesis of recurrent spontaneous abortion. The aim of this study was to identify the differentially expressed genes (DEGs) and pathways in recurrent spontaneous abortion. MATERIAL AND METHODS Gene expression data series of GSE22490 and GSE26787 were obtained from the GEO database to identify the differentially expressed genes between patients with recurrent miscarriage (Case group) and patients with uncomplicated pregnancies matched for gestational age (Control group). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEEG) were applied to enrich the biological functions and pathways of the identified differentially expressed genes. A protein-protein interaction (PPI) network was constructed thorough the STRING database. Thirty-one cases of recurrent spontaneous abortion (Case group) and 30 cases of artificial abortion (Control group) were included in the study. The protein expression of hub genes in the villi and decidua tissue of the 2 groups was detected by immunohistochemical assay. RESULTS Forty-six DEGs were identified with the enriched biological function mainly in the aspects of glutamate secretion and positive regulation of synapse assembly. KEGG pathway analysis indicated the dysregulated genes were only enriched in the glutamatergic synapse pathway. In the PPI network, 83 nodes and 273 edges with the average node degreed of 6.58 were enriched. The hub gene (ATP6V1G3) of the included 46 genes was identified using Cytohubba software. In the Case group, the high expression of ATP6V1G3 protein was detected in 13 (43.3%) and 10 (33.3%) for placental villus and decidual tissue, respectively. However, the high expression rate in the Control group was 23.3% and 16.7% for placental villus and decidual tissue, respectively. The ATP6V1G3 protein high expression rate was not significantly different between the Case and Control groups (P>0.05). CONCLUSIONS We found differential gene expression profiles in villous and decidual tissues between patients with recurrent miscarriage vs. those with uncomplicated pregnancies. Upregulation of the ATP6V1G3 gene may play an important role in the development of recurrent miscarriage.
背景 复发性自然流产的分子机制尚不清楚。有研究表明，基因失调参与了复发性自然流产的发病过程。本研究旨在识别复发性自然流产中差异表达基因（DEGs）及相关通路。
材料与方法 从基因表达综合数据库（GEO数据库）获取GSE22490和GSE26787基因表达数据系列，以识别复发性流产患者（病例组）与孕周匹配的正常妊娠患者（对照组）之间的差异表达基因。运用基因本体论（GO）和京都基因与基因组百科全书（KEGG）对鉴定出的差异表达基因的生物学功能和通路进行富集分析。通过STRING数据库构建蛋白质-蛋白质相互作用（PPI）网络。本研究纳入31例复发性自然流产患者（病例组）和30例人工流产患者（对照组）。采用免疫组织化学法检测两组绒毛和蜕膜组织中核心基因的蛋白表达。
结果 共鉴定出46个差异表达基因，其富集的生物学功能主要集中在谷氨酸分泌和突触组装的正调控方面。KEGG通路分析表明，失调基因仅富集于谷氨酸能突触通路。在PPI网络中，共富集到83个节点和273条边，平均节点度为6.58。使用Cytohubba软件从46个基因中鉴定出核心基因（ATP6V1G3）。病例组中，胎盘绒毛和蜕膜组织中ATP6V1G蛋白高表达率分别为13例（43.3%）和10例（33.3%）。而对照组胎盘绒毛和蜕膜组织中的高表达率分别为23.3%和16.7%。病例组与对照组ATP6V1G3蛋白高表达率差异无统计学意义（P>0.05）。
结论 我们发现复发性流产患者与正常妊娠患者的绒毛和蜕膜组织中存在差异基因表达谱。ATP6V1G3基因上调可能在复发性流产的发生发展中起重要作用。
