Uterine spiral artery remodeling is one of the key maternal adaptations of pregnancy, allowing delivery of the large volumes of maternal blood required for both placental and fetal growth. Failure of this process is associated with obstetric complications including preeclampsia, fetal growth restriction and miscarriage. Spiral artery remodeling is characterized by loss of the musculoelastic wall which is replaced by fibrinoid and intramural extravillous trophoblast cells (EVT). In recent years attention has focused on the initial stages of spiral artery remodeling which include separation of the vascular smooth muscle cells (VSMCs) and their phenotypic switch to a more synthetic phenotype, facilitating their migration away from the vessel wall. However, less is known about the final fate of the VSMCs. In vitro studies suggested that EVT could induce VSMC apoptosis, though VSMC apoptosis is not seen within the wall of the spiral arteries undergoing remodeling. However, apoptotic VSMCs have been observed amongst those cells which had migrated away from the vessel wall, a process associated with the presence of EVT. In the current study we aimed to further explore the mechanism by which EVT induce VSMC apoptosis. Primary cultures of first trimester EVT were established and EVT exosomes (EVT-exo) isolated from the culture medium (CM). Both EVT-CM and EVT-exo induced VSMC apoptosis, the effect of EVT-CM was abrogated by an exosome blocker. EVT-exo uptake was observed in VSMCs In silico analysis suggested several potential miR species may be involved, of which overexpression of miR-143-3p in VSMCs induced their apoptosis. miR-143-3p overexpression by EVT, also led to overexpression in EVT-exo, which in turn induced higher rates of VSMC apoptosis than seen in controls. These data suggest that miR-143-3p packaged in EVT-exo induces VSMC apoptosis and may be critical for the final stages of spiral artery remodeling and establishment of a successful pregnancy.