Identification of genes and miRNA associated with idiopathic recurrent pregnancy loss: an exploratory data mining study

Abstract

Background: Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication, with an incompletely understood pathology. While many entities were proposed to elucidate the pathogenic basis of RPL, only few were significant enough to warrant investigation in all affected couples.. The aim of this study was to provide novel insights into the biological characteristics and related pathways of differentially expressed miRNA (DEMs) and genes (DEGs), in RPL, and construct a molecular miRNAs-mRNAs network. Methods: miRNAs and gene expression data were collected, and a number of DEMs and (DEGs) were obtained, and regulatory co-expression network were constructed. Function and enrichment analyses of DEMs were conducted using DIANA-miRPath. DEGs were screened, and were used in generation of protein-protein interaction (PPI) network, using STRING online database. Modularity analysis, and pathway identification operations were used in identifying graph clusters and associated pathways. DEGs were also used for further gene ontology (GO) analysis, followed by analysis of KEGG pathway. Results: A total of 34 DEMs were identified, and were found to be highly enriched in TGF-β signaling pathway, Fatty acid metabolism and TNF signaling pathway. Hub miRNAs were selected and were found to be involved in several functional pathways including progesterone-mediated oocyte maturation and Thyroid hormone signaling pathway. Five dysregulated feedback loops involving miRNA and TFs were identified and characterized. Most notably, PPI network analysis identified hub-bottleneck protein panel. These appear to offer potential candidate biomarker pattern for RPL diagnosis and treatment. Conclusions: The present study provides novel insights into the molecular mechanisms underlying RPL.

Associations between the exposure to organophosphate flame retardants during early pregnancy and the risk of spontaneous abortion based on metabolomics combined with tandem mass spectrometry

“…There are many factors that affect early pregnancy abortion. Numerous investigations have indicated that chromosomal abnormalities, antiphospholipid syndrome, congenital structural abnormalities of the uterus, type I diabetes, and thyroid dysfunction may lead to spontaneous abortion in early pregnancy (2). However, other than these known risk factors, still almost half of the cause spontaneous abortion are unclear and further explanation is urgently needed.…”

Non‐coding RNAs and their cross‐talks impacting reproductive health of women

“…In another study, 34 differentially expressed miRNAs were reported in EPL, which were found to be enriched in several regulatory pathways, including TNF and TGF‐β signaling pathways. A study reported changes in expression of miR‐378a‐3p and miR‐371a‐5p modulating apoptotic pathways associated with EPL and RPL, respectively (Bahia et al, 2020; E. Du, Cao, et al, 2019; Hong et al, 2018). Yang et al (2018) also reported deregulated expression of several miRNAs leading to irregularity in non‐invasiveness in recurrent miscarriage, leading to pregnancy loss.…”

Down-Regulation of circulating miR-23a-3p, miR-101-3p, and miR-let-7c in Women with Idiopathic Recurrent Pregnancy Loss

“…Emerging evidence also suggests that microRNAs are key regulators of maternal-fetal communication during pregnancy, and can play a fundamental roles in blastocyst implantation, embryonic development and maintenance of pregnancy [17][18][19]. Altered expression levels of miRNAs have been reported in various pathophysiological conditions, including idiopathic recurrent pregnancy loss (iRPL) [20,21]. In addition to being are expressed in different cell types and tissues, miRNAs are released in extracellular body uids such as plasma, serum, urine, tears, saliva and seminal uid [22].…”