Proteomic Epithelial-To-Mesenchymal Transition Signature in Fetoplacental Small Extracellular Vesicles of Early-Onset Preeclampsia.

Preeclampsia (PE), a hypertensive disorder in pregnancy, is linked to placental vascular remodelling, increasing risks of foetal growth restriction and long-term offspring health problems. The role of fetoplacental endothelial cell-derived extracellular vesicles (EVs) in PE remains underexplored. This study investigates whether EV composition in Early-Onset PE (EO-PE) is altered, potentially contributing to impaired foetal development. Small EVs (sEVs) were isolated from primary fetoplacental endothelial cells (fpECs) of term (T), preterm (PT) and EO-PE pregnancies. sEVs were characterised using transmission electron microscopy, nanoparticle tracking analysis and Western blotting, confirming spherical morphology, size (<200 nm) and expression of canonical EV and endothelial markers. Proteomic profiling via nano-LC MS/MS and gene set enrichment analysis revealed a cohesive proteomic profile in fpEC-derived T- and PT-sEVs, but EO-PE-derived sEVs showed heterogeneity and functional alterations compared to T- and PT-derived sEVs. Notably, EO-PE-sEVs were enriched in proteins affiliated to epithelial-to-mesenchymal transition and myogenesis, processes tied to tissue remodelling and vascular homeostasis, all hallmarks in PE. This signature may represent a molecular signal associated with endothelial dysfunction. In contrast, T-sEVs were enriched in cell cycle and DNA repair pathways. These findings underscore the role of fetoplacental-derived EVs in placental-foetal communication under pathophysiological conditions.