Gestational week 13 - a critical window for pre-eclampsia pathogenesis: A cell-free RNA gene expression study

Pre-eclampsia (PE) is a hypertensive pregnancy disorder associated with significant maternal and foetal morbidity, with symptoms typically emerging late, highlighting the need to identify early molecular changes for effective screening and management.

We analysed 228 maternal plasma cfRNA samples from GSE154377 and GSE192902 spanning GW8-16 for gestational-week-specific differential expression. We additionally analysed available later-gestation samples in three windows, 17-20, 24-26, and 27-39 weeks, using the same differential expression framework. Differential expression was assessed using DESeq2, with Gene Ontology (GO) and KEGG pathway enrichment and long non-coding RNAs (lncRNAs) and small nucleolar RNAs (snoRNAs). characterisation, alongside severity comparisons across normotensive, PE, and severe PE groups.

A major transcriptomic shift occurred at GW 13, with 2894 differentially expressed genes, highlighting immune activation, mitochondrial regulation, apoptosis, and NOD-like receptor and Th1/Th2 signalling pathways. Non-coding RNAs (ncRNA), particularly lncRNAs and snoRNAs, were strongly implicated in immune dysregulation and vascular dysfunction. Key genes, including MYZAP, CAV2, OXTR, and GBP1, emerged as potential early biomarkers, while later gestation showed fewer DEGs and less transcriptomic disruption than GW 13, with stronger changes observed in severe PE.

GW 13 represents a critical molecular window for PE pathogenesis, while cfRNA profiling offers a non-invasive approach to detect early changes and support first-trimester screening strategies, pending prospective validation. The identification of regulatory ncRNA and protein-coding biomarkers offers translational opportunities for diagnostics and targeted interventions to improve maternal-foetal outcomes.