In vitro activation of microglia cells by extracellular vesicles from women with preeclampsia

Preeclampsia (PE) is a condition characterized by de novo high blood pressure and organ damage after the 20th week of pregnancy. PE has been related to the occurrence of neurologic issues, but the mechanisms behind this remain unknown. The human placenta secretes high amounts of extracellular vesicles (EVs), which reach the maternal periphery and are increased in PE. EVs are membrane-delimited particles carrying various bioactive molecules, and mediate intercellular communication between distal organs. The transport of signals from the placenta to the brain is hindered by the blood-brain barrier (BBB), which prevents neurotoxic plasma macromolecules, blood cells, and pathogens, among others, from entering the brain. However, EVs can penetrate the BBB and reach the central nervous system, where they can be internalized by microglia cells, the tissue-resident macrophages. Changes in microglia are linked to brain dysfunction, therefore understanding the communication between the placenta and the brain during PE is necessary for developing therapeutic tools to prevent the risk of PE-related brain damage. In this thesis, the effect of plasma EVs from controls and PE patients on microglial cells was evaluated in an in vitro setting.The results provided by this thesis provided a preliminary understanding of the interactions between the placenta and microglia cells. We proved HMC3 cells could uptake both the sEVs derived from NP and PE women. After the uptake of both NP or PE-derived sEVs, the expressions and transcriptions of representative surface marker CD11b and IBA1 were all upregulated and indicated an activated state of microglia cells. Moreover, the typical miRNAs in sEVs were also upregulated in HMC3 cells after the incubation, especially in the group treated with PE-derived sEVs for 0.5 h. Further research is required to fully understand the mechanisms underlying these effects and their potential implications for neurological diseases and conditions.