Integrative analysis of circulating microRNAs and the placental transcriptome in recurrent pregnancy loss

Abstract

Recurrent pregnancy loss (RPL) is a major type of pathological pregnancy that still lacks reliable early diagnosis and effective treatment. The placenta is critical to fetal development and pregnancy success because it participates in critical processes such as early embryo implantation, vascular remodeling, and immunological tolerance. RPL is associated with abnormalities in the biological behavior of placental villous trophoblasts, resulting in aberrant placental function. MicroRNAs (miRNAs) are increasingly being recognized as essential regulators of placental development, as well as potential biomarkers. In this study, plasma miRNAs and placental messenger RNAs (mRNAs) from RPL patients and normal pregnant (NP) controls were sequenced and analyzed. Compared to those in NP controls, 108 circulating miRNAs and 1199 placental mRNAs were differentially expressed in RPL samples. A total of 140 overlapping genes (overlapping between plasma miRNA target genes and actual placental disorder genes) were identified, and functional enrichment analysis showed that these genes were mainly related to cell proliferation, angiogenesis, and cell migration. The regulatory network among miRNAs, overlapping genes, and downstream biological processes was analyzed by protein–protein interactions and Cytoscape. Moreover, enriched mRNAs, which were predictive targets of the differentially expressed plasma miRNAs miR-766-5p, miR-1285-3p, and miR-520a-3p, were accordingly altered in the placenta. These results suggest that circulating miRNAs may be involved in the pathogenesis of RPL and are potential noninvasive biomarkers for RPL.

The Expression of microRNAs and Their Involvement in Recurrent Pregnancy Loss

“…The use of circulating miRNAs in the blood as biomarkers of recurrent miscarriages was also supported by Yang et al Among all the miRNAs, the researchers focused on increased expression of miR-100-5p in the blood of women with recurrent miscarriages [ 28 ]. This finding is supported by the results of other studies too; hence, the authors propose that the expression of miR-100-5p might be useful not only as a diagnostic and prognostic biomarker for recurrent miscarriages but also for predicting the outcome of IVF attempts [ 15 , 20 , 31 ].…”

RETRACTED ARTICLE: Exposure to pesticide components causes recurrent pregnancy loss by increasing placental oxidative stress and apoptosis: a case–control study

“…Exclusion criteria : women were excluded once they showed any systemic diseases or other possible causes of RPL such as endocrine disorders, uterine problems, immune-inflammatory diseases, possible chromosomal aberrations (family history), and infections such as TORCH infections 13 .…”

Bioinformatics analysis and validation of differentially expressed miRNA in the sperm of partners of patients with unexplained recurrent miscarriages

“…In the target gene prediction results, hsa-miR-1285-3p, hsa-miR-486-3p, and hsa-miR-146b-3p obtained high scores. These miRNAs are expressed in the placenta, trophoblasts, and embryo [11,12,13]. Their downstream target genes, JUN, HDAC2, TP53, and FGFR3, are involved in fertilisation, early embryonic development, and other processes [14,15,16,17].…”