BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication with elusive pathogenesis. Although epigenetic dysregulation is implicated, its layer-specific placental roles are poorly defined. This study aimed to identify shared and layer-specific epigenetic alterations in PE by profiling DNA methylation and gene expression in placental villi (PV) and chorioamniotic membranes (CAM). RESEARCH DESIGN AND METHODS: PV and CAM samples were collected from 7 normal and 8 PE pregnancies, and three public DNA methylation datasets (GSE98224, GSE44667, GSE75196) were integrated. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified based on whole-genome methylation and transcriptome sequencing. Layer-specific and shared gene sets were identified by cross-analysis, with functional annotation using Gene Ontology (GO). RESULTS: EM-seq revealed a hypermethylation-dominant, tissue-specific methylation landscape in PE placentas. Cross-tissue comparison identified shared DMGs between the two layers, including nine key genes consistently altered in public datasets. Integrated analysis in PV further identified 22 co-dysregulated genes, enriched in thermoregulation, maternal-fetal immunity, signal transduction, and cell differentiation. CONCLUSIONS: This study elucidates the shared and layer-specific dysregulation of gene networks at methylomic and transcriptomic levels in PE placenta. Comparing PV and CAM highlights placental epigenetic heterogeneity and dysfunction, offering novel clues for mechanistic research and layer-targeted therapies.
Liu et al. (Mon,) studied this question.