Early Prediction of Preeclampsia Based on Transposable Elements Deregulation in the Placenta [RNA-Seq]

Preeclampsia (PE) is a pregnancy-associated hypertension disorder which affects 5–10% of pregnant women each year worldwide, which leads to adverse maternal and child outcomes. PE remains inadequately predicted, prevented and treated. Here we investigated the epigenetic alterations contributing to PE. We found an increase in histone acetylation levels across transposable elements (TEs) in the preeclamptic placenta. Histone hyperacetylation in PE is associated with an increased expression of endogenous retrovirus (ERV) and long interspersed nuclear element 1 (L1, LINE1) subfamilies of TEs in five independent pregnancy cohorts. A higher level of TE RNAs correlates with an elevated type I interferon (IFN-I) pathway, suggesting inflammation associated with PE could be due to the sensing of TE transcripts by the antiviral innate immune system. Furthermore, TE-focused analysis of maternal cell-free RNA (cfRNA) data revealed differential levels of TE subfamilies in PE compared to healthy controls. Training TE transcript signatures for PE prediction showed a robust performance of area under the curve (AUC) of 0.96, with validation cohort AUC of 0.88 with 81% sensitivity and 74% positive predictive value (PPV). Overall, these findings show TE deregulation is associated with PE pathology and analysis of TE levels in maternal cfRNA is an exciting approach for early diagnosis of PE, which can improve prophylaxis, obstetric and neonatal outcomes.