Ye Zhuang, Meng Qingxue, Zhang Weiwen, He Junli, Zhao Huanyi, Yu Chengwei, Liang Weizheng, Li Xiushen, Wang Hao
Department of Rheumatology, The First Hospital of Jilin University, Changchun, China.
Department of Pediatrics, Shenzhen University General Hospital, Shenzhen, China.
Front Vet Sci. 2022 May 6;9:867405. doi: 10.3389/fvets.2022.867405. eCollection 2022.
Endometriosis (EMs) is a common benign gynecological disease in women of childbearing age, which usually causes pelvic pain, secondary dysmenorrhea, and infertility. EMs has been linked to recurrent pregnancy loss (RPL) in epidemiological data. The relationship of both, however, remains unknown. The purpose of this study is to explore the underlying pathological mechanisms between EMs and RPL. We searched Gene Expression Omnibus (GEO) database to obtain omics data of EMs and RPL. Co-expression modules for EMs and RPL were investigated by using weighted gene co-expression network analysis (WGCNA). The intersections of gene modules with the strong correlation to EMs or RPL obtained by WGCNA analysis were considered as shared genes. MicroRNAs (miRNAs) and their corresponding target genes linked to EMs and RPL were found though the Human MicroRNA Disease Database (HMDD) and the miRTarbase database. Finally, we constructed miRNAs-mRNAs regulatory networks associated with the two disorders by using the intersection of previously obtained target genes and shared genes. We discovered as significant modules for EMs and RPL, respectively, by WGCNA. The energy metabolism might be the common pathogenic mechanism of EMs and RPL, according to the findings of a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We discovered several target genes that might be linked to these two disorders, as well as the potential mechanisms. RAB8B, GNAQ, H2AFZ, SUGT1, and LEO1 could be therapeutic candidates for RPL and EMs. The PI3K-Akt signaling pathway and platelet activation were potentially involved in the mechanisms of EM-induced RPL. Our findings for the first time revealed the underlying pathological mechanisms of EM-induced RPL and identified several useful biomarkers and potential therapeutic targets.
子宫内膜异位症(EMs)是育龄期女性常见的良性妇科疾病,通常会导致盆腔疼痛、继发性痛经和不孕。在流行病学数据中,EMs与复发性流产(RPL)有关。然而,两者之间的关系尚不清楚。本研究的目的是探讨EMs与RPL之间潜在的病理机制。我们搜索了基因表达综合数据库(GEO)以获取EMs和RPL的组学数据。通过加权基因共表达网络分析(WGCNA)研究EMs和RPL的共表达模块。将通过WGCNA分析获得的与EMs或RPL高度相关的基因模块的交集视为共享基因。通过人类微小RNA疾病数据库(HMDD)和miRTarbase数据库发现与EMs和RPL相关的微小RNA(miRNAs)及其相应的靶基因。最后,我们利用先前获得的靶基因和共享基因的交集构建了与这两种疾病相关的miRNAs - mRNAs调控网络。通过WGCNA分别发现了EMs和RPL的重要模块。根据京都基因与基因组百科全书(KEGG)富集分析的结果,能量代谢可能是EMs和RPL的共同致病机制。我们发现了几个可能与这两种疾病相关的靶基因以及潜在机制。RAB8B、GNAQ、H2AFZ、SUGT1和LEO1可能是RPL和EMs的治疗候选靶点。PI3K - Akt信号通路和血小板活化可能参与了EMs诱导RPL的机制。我们的研究结果首次揭示了EMs诱导RPL的潜在病理机制,并确定了几个有用的生物标志物和潜在的治疗靶点。