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 fetal 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 PE is altered, potentially contributing to impaired fetal development. Small EVs (sEVs) were isolated from primary fetoplacental endothelial cells (fpECs) of term (T), preterm (PT), and early-onset PE (EO-PE) pregnancies. sEVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting, confirming spherical morphology, size (<200nm), and expression of canonical EV and endothelial markers. Proteomic profiling via nano-LC MS/MS and gene set enrichment analysis revealed consistent proteomes in fpEC-derived 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 linked to epithelial-to-mesenchymal transition and myogenesis, processes tied to tissue remodelling and vascular homeostasis, all hallmarks in PE. This signature may transmit signals of endothelial dysfunction to the fetus. In contrast, T-sEVs were enriched in cell cycle and DNA repair pathways. These findings underscore the role of fetoplacental-derived EVs in placental-fetal communication under pathophysiological conditions.