Placenta-derived extracellular vesicles in fetal health: emerging insights into brain development and environmental interactions.

Placenta-derived extracellular vesicles (EVs) are emerging as critical regulators of maternal-fetal communication during pregnancy. These lipid bilayer-enclosed particles, primarily secreted by trophoblasts, transport bioactive cargos-including RNAs, proteins, lipids and neurotransmitters-that influence a wide range of developmental and immunological processes. While much attention has been given to their roles in maternal adaptation and health outcomes, recent studies highlight their direct impact on fetal development, particularly fetal brain development. Emerging evidence suggests that placental EVs may traverse both the placental and blood-brain barriers, thereby contributing to signaling processes that influence neurogenesis, cell fate specification and regional brain patterning. Their cargo composition is dynamic, modulated by gestational age and environmental factors such as air pollution, viral infection and chemical toxicants. These stressors can alter EV secretion and molecular content, contributing to adverse fetal outcomes including impaired organogenesis and neurodevelopmental delays. In this review, we synthesize current knowledge on placental EV biology, examine their roles in maternal and fetal health with an emphasis on neurodevelopment and evaluate how environmental exposures reshape EV-mediated signaling. We also discuss emerging technologies and translational opportunities, including EV-based diagnostics and therapeutic delivery systems. Collectively, placenta-derived EVs represent a vital yet underexplored mechanism in fetal programming, offering novel insights into the developmental origins of health and disease.