A successful pregnancy depends on a precise interaction between trophoblast cells of fetal origin and maternal endothelial and immune cells. Approximately one third of all pregnancies are affected by disorders related with inappropriate vessel transformation and abnormal trophoblast invasion. In most of the cases, the causes and treatments remain elusive.
MicroRNAs (miRNAs) are a new class of non-coding RNAs which are associated with the control of important cellular processes including proliferation, invasion and differentiation. Human placenta exhibits a tissue-specific miRNA expression profile which dynamically changes throughout pregnancy and whose dysregulation is found in pregnancy pathologies. Trophoblast cells secrete Extracellular Vesicles (EVs) into the maternal bloodstream, and their content resembles those of their origin cells.
We hypothesize that trophoblast cells communicate with maternal cells by release of EVs containing placental miRNAs. Levels of EVs and miRNAs may be altered in pregnancy disorders having the potential to serve as a non-invasive diagnostic tool.
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.