EV-microRNA signatures in pregnant women with idiopathic recurrent pregnancy loss: deciphering microRNAome pathway networks at feto-maternal interface

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 12, 2025

Background Despite extensive research in the past decade, exact pathogenesis of recurrent pregnancy loss (RPL) remains unknown. At time pregnancy, human placenta releases microRNAs (miRNAs) enclosed extracellular vesicles (EVs), which enter into maternal circulation and play an important role at feto-maternal interface to sustain a successful pregnancy. Aberrant expression these miRNAs often results adverse complications. Therefore, studying EV-miRNAs could provide insights RPL. Methods The present study included idiopathic currently pregnant (<22 weeks gestation) RPL women (n=10) gestational-age-matched healthy as control (n=5). EVs were isolated from plasma samples characterized for their morphology cell-surface marker. Total RNA was subjected miRNA sequencing on Illumina NovaSeq 6000 platform. Differentially expressed (DE) identified using DESeq package. Target prediction pathway analysis done TargetScan, miRDB, miRTarBase, DIANA-miRPath v3.0 online tool. Protein–protein interaction STRING, hub genes Cytoscape software. Results revealed 66 (44 known 22 novel) significantly DE between women. Among these, 37 downregulated 29 upregulated, log2|FC| ≥ 1. Network-based showed highest degree nine (hsa-miR-155-5p, hsa-miR-26a-5p, hsa-miR-204-5p, hsa-miR-140-5p, hsa-miR-139-5p, hsa-let-7e-5p, hsa-miR-149-5p, hsa-miR-374a-5p, hsa-miR-190a-5p). Gene Ontology (GO) KEGG target significant involvement Hippo, FoxO, TGF-β, p53 signaling pathways, crucial Top 10 ( NFKB1 , IL6 JUN FOS CXCL8 PTGS2 TGFB1 MMP9 STAT1 CD4 ) enriched immunological pathways—Th1/Th2/Th17 differentiation, NF-κB pathway, TNF-α signaling, IL-17 vascular endothelial growth factor VEGF pathway. Conclusion These suggest that circulating blood clinical dysregulated molecular pathways interface.

Language: Английский

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Exploring Differentially Expressed Sperm miRNAs in Idiopathic Recurrent Pregnancy Loss and Their Association with Early Embryonic Development

Non-Coding RNA, Journal Year: 2024, Volume and Issue: 10(4), P. 41 - 41

Published: July 21, 2024

The high incidence of idiopathic recurrent pregnancy loss (iRPL) may stem from the limited research on male contributory factors. Many studies suggest that sperm DNA fragmentation and oxidative stress contribute to iRPL, but their roles are still debated. MicroRNAs (miRNAs) short non-coding RNAs regulate various biological processes by modulating gene expression. While differential expression specific miRNAs has been observed in women suffering miscarriages, paternal remain unexplored. We hypothesize analyzing can provide crucial insights into pathophysiology iRPL. Therefore, this study aims identify dysregulated spermatozoa partners iRPL patients. Total mRNA was extracted samples control groups, followed miRNA library preparation high-output sequencing. Subsequently, raw sequence reads were processed for analysis, target prediction, bioinformatics analysis. Twelve differentially expressed identified group, with eight upregulated (hsa-miR-4454, hsa-miR-142-3p, hsa-miR-145-5p, hsa-miR-1290, hsa-miR-1246, hsa-miR-7977, hsa-miR-449c-5p, hsa-miR-92b-3p) four downregulated (hsa-miR-29c-3p, hsa-miR-30b-5p, hsa-miR-519a-2-5p, hsa-miR-520b-5p). Functional enrichment analysis revealed targets involved closely associated quality embryonic development.

Language: Английский

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Identification and RT-qPCR Validation of Biomarkers Based on Butyrate Metabolism-Related Genes to Predict Recurrent Miscarriage

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 6917 - 6934

Published: Oct. 1, 2024

To date, the cause of recurrent miscarriage (RM) in at least 50% patients remains unknown. However, no study has explored correlation between butyrate metabolism-related genes (BMRGs) and RM.

Language: Английский

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Association of the miR-143 Gene rs353292 Polymorphism with Recurrent Pregnancy Loss in Caucasian Women: A Novel Finding in a Multifactorial Devastating Problem

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11952 - 11952

Published: Nov. 7, 2024

The purpose of this prospective case-control study is to investigate the correlation miR-143 gene rs353292 polymorphism in Caucasian women with recurrent pregnancy loss (RPL) compared a matched control group at least one live birth and without losses. In total, 110 losses 95 were recruited. Peripheral blood was collected from all women, isolation DNA performed Monarch Genomic Purification. Polymerase chain reaction applied amplify sequence promoter, carrying rs353292. incidence genotype CC RPL statistically significantly higher than (

Language: Английский

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