Roles of placenta/placenta-derived extracellular vesicles on brain development

Placental trophoblasts are a major cell type of placenta and play important roles in many critical processes during pregnancy, including implantation, hormone production and regulation, immune protection of the fetus, and nutrient supply. The cells also play an important role in mediating the communication between the mother and the fetus including fetal brain development. The cells actively release extracellular vesicles (EVs), nano-sized (.05-1 μm) membrane-bound vesicles, into the maternal and the fetal circulation. EVs shuttle cargoes of bioactive molecules, such as proteins, lipids, and nucleic acids, from trophoblasts to the recipient cells, modifying gene expression and biology in the cells. Growing evidence indicates that EVs reach fetal neural cells after crossing the blood-brain barrier (BBB). However, it is not known whether metal exposure during pregnancy affects the production, release, and/or cargoes of placental EVs and how these changes lead to divergent neurodevelopmental outcomes. We hypothesize that maternal metal exposure modifies the production/release and/or cargoes of placental EVs, which in turn, affects fetal brain development. To test this hypothesis, we are conducting experiments:

1. To identify altered EV cargoes (proteins and RNAs) in response to metal exposure
2. To determine roles of placental EVs on NSC function in the absence or presence of metal exposure

I anticipate that different metal treatment will differentially affect cargoes in EVs of trophoblasts. By comparing the EV cargo changes between individual metals, I anticipate to identify both unique and common EV cargoes among the metals. Furthermore, we will for the first time identify EV cargoes that are impacted by the treatment of metal mixtures. These profiling studies will likely generate new hypotheses regarding the mechanisms through which metal exposures may affect neural function via altered placental EV cargoes.

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