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

Area of Science:

• Obstetrics and Gynecology
• Vascular Biology
• Perinatal Medicine

Background:

• Preeclampsia (PE) is a pregnancy hypertensive disorder associated with placental vascular remodeling and adverse fetal outcomes.
• Fetoplacental endothelial cell-derived extracellular vesicles (EVs) are implicated in placental-fetal communication, but their role in PE is not well understood.
• Early-onset PE (EO-PE) presents a critical window to investigate EV alterations.

Purpose of the Study:

• To investigate the proteomic composition and functional alterations of small EVs (sEVs) derived from fetoplacental endothelial cells (fpECs) in EO-PE pregnancies.
• To determine if altered sEV composition in EO-PE contributes to impaired fetal development.

Main Methods:

• Isolation and characterization of sEVs from primary fpECs of term (T), preterm (PT), and EO-PE pregnancies using electron microscopy, nanoparticle tracking analysis, and Western blotting.
• Proteomic profiling of sEVs using nano-LC-MS/MS.
• Gene set enrichment analysis to identify functional pathways.

Main Results:

• fpEC-derived sEVs from T and PT pregnancies exhibited cohesive proteomic profiles.
• EO-PE-derived sEVs displayed heterogeneity and functional alterations compared to T- and PT-sEVs.
• EO-PE-sEVs were enriched in proteins related to epithelial-to-mesenchymal transition and myogenesis, suggesting a link to endothelial dysfunction and tissue remodeling.

Conclusions:

• Fetoplacental endothelial cell-derived sEVs exhibit distinct proteomic signatures in EO-PE.
• These altered sEVs may serve as molecular signals contributing to endothelial dysfunction and impacting fetal development in PE.
• EVs play a crucial role in pathophysiological placental-fetal communication.