Transcriptome‐wide high‐throughput m 6 A sequencing of differential m 6 A methylation patterns in the decidual tissues from RSA patients

Abstract Recurrent spontaneous abortion (RSA) is characterized by two or more consecutive pregnancy losses in the first trimester of pregnancy, experienced by 5% of women during their reproductive age. As a complex pathological process, the etiology of RSA remains poorly understood. Recent studies have established that gene expression changes dramatically in human endometrial stromal cells (ESCs) during decidualization. N6‐methyladenosine (m 6 A) modification is the most prevalent epigenetic modification of mRNA in eukaryotic cells and it is closely related to the occurrence and development of many pathophysiological phenomena. In this study, we first confirmed that high levels of m 6 A mRNA methylation in decidual tissues are associated with RSA. Then, we used m 6 A‐modified RNA immunoprecipitation sequence (m 6 A‐seq) and RNA sequence (RNA‐seq) to identify the differentially expressed m 6 A methylation in decidual tissues from RSA patients and identified the key genes involved in abnormal decidualization by bioinformatics analysis. Using m 6 A‐seq, we identified a total of 2169 genes with differentially expressed m 6 A methylation, of which 735 m 6 A hypermethylated genes and 1434 m 6 A hypomethylated genes were identified. Further joint analysis of m 6 A‐seq and RNA‐seq revealed that 133 genes were m 6 A modified with mRNA expression. GO and KEGG analyses indicated that these unique genes were mainly enriched in environmental information processing pathways, including the cytokine–cytokine receptor interaction and PI3K‐Akt signaling pathway. In summary, this study uncovered the transcriptome‐wide m 6 A modification pattern in decidual tissue of RSA, which provides a theoretical basis for further research into m 6 A modification and new therapeutic strategies for RSA.