Altered 5‐methylcytosine modification of mRNA is involved in the pathogenesis of pre‐eclampsia

5-Methylcytosine (m⁵ C) is a prevalent RNA modification in messenger RNAs (mRNAs). Despite its abundance, its role in the decidua of pre-eclampsia (PE) remains elusive. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing (RNA-seq) to map m⁵ C peaks and mRNA expression profile in the decidua of human early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses elucidated potential roles of the differentially methylated mRNAs (DMGs) and differentially expressed mRNAs in decidualization pathways. Integrative analysis of MeRIP-seq and RNA-seq data pinpointed 50 candidate genes linked to PE, marked by both differentially methylated m⁵ C peaks and congruent expression changes. To validate these observations, we selected nine genes for verification via quantitative PCR. Our results underscore the precision and reproducibility of our bioinformatics approach. Importantly, we propose that changes in m⁵ C modification and expression of relevant mRNA might influence the pathogenesis of PE by hampering decidualization. This work shines light on the distinct mRNA m⁵ C modification patterns and expression profiles in the decidua of PE, implicating pivotal signaling disruptions and decidualization impediments in the onset of PE.