During pregnancy, biochemical and structural changes in the brain adapt maternal physiology and behavior to ensure offspring survival. Remarkably, little is known about the molecular and cellular mechanisms that govern these processes and how they are influenced by pregnancy pathologies. Placental cells release extracellular vesicles (EVs) into the maternal blood as a mechanism of maternal-fetal communication. Although evidence shows that placental EVs mediate immune tolerance and cardiovascular adaptations in the maternal organism, their functions in the nervous system remains to be investigated. We hypothesize that placental EVs induce changes in the blood brain barrier (BBB) and modulate microglia cell responses. Moreover, these EVs may be the missing link between the placenta and neurologic manifestations of pre-eclampsia. A 3D BBB model in a microfluidic biochip will be employed to investigate BBB structure and properties under the effects of healthy and pre-eclamptic placental EVs. Additionally, mechanisms of placental EV uptake by microglia cells and their activation will be investigated. This proposal strengths a new research field in our group focused on understanding the biological mechanisms involved in the communication between placenta and brain in normal and pathological human pregnancies.