DNA methylation profiling in recurrent miscarriage

Abstract

Recurrent miscarriage (RM) is a complex clinical problem. However, specific diagnostic biomarkers and candidate regulatory targets have not yet been identified. To explore RM-related biological markers and processes, we performed a genome-wide DNA methylation analysis using the Illumina Infinium HumanMethylation450 array platform. Methylation variable positions and differentially methylated regions (DMRs) were selected using the Limma package in R language. Thereafter, gene ontology (GO) enrichment analysis and pathway enrichment analysis were performed on these DMRs. A total of 1,799 DMRs were filtered out between patients with RM and healthy pregnant women. The GO terms were mainly related to system development, plasma membrane part, and sequence-specific DNA binding, while the enriched pathways included cell adhesion molecules, type I diabetes mellitus, and ECM–receptor interactions. In addition, genes, including ABR, ALCAM, HLA-E, HLA-G, and ISG15, were obtained. These genes may be potential candidates for diagnostic biomarkers and possible regulatory targets in RM. We then detected the mRNA expression levels of the candidate genes. The mRNA expression levels of the candidate genes in the RM group were significantly higher than those in the control group. However, additional research is still required to confirm their potential roles in the occurrence of RM.

Abnormal methylation of PRDM16 and PTPRN2 genes in chorionic villi in miscarriage

“…Ген PRDM16 является импринтированным с экспрессией с отцовского аллеля [30]. Дифференциальное метилирование гена PRDM16 было обнаружено в образцах децидуального эпителия матки, полученного путем выскабливания, у женщин с привычным невынашиванием беременности [31]. Все это указывает на возможное влияние уровня метилирования гена PRDM16 у матери на нормальное развитие потомства.…”

Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration

“…Li et al. conducted a genome-wide screening of DNA methylation in decidual samples from women with RPL ( 54 ). The findings showed that the differentially methylated genes ( PRDM16 , HLA-E , HLA-G , and ISG15 ) were closely related to embryonic development ( 55 – 57 ).…”

“…Li et al. also verified the upregulated expression of ISG15 in RPL by utilizing RNA-seq technology, and these authors found that ISG15 was involved in the type I interferon signaling pathway by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses ( 54 ). CREB5 regulates cell growth, proliferation, differentiation and the cell cycle and belongs to the cAMP response element ( CRE )-binding protein family ( 58 ).…”