Maternal communication of stressful signals via extracellular vesicles

MONTELEONE, MELISA C; BILLI, SILVIA; FERNÁNDEZ, ELIANA MAILÉN; BROCCO MARCELA ADRIANA

Congreso; IFPA 2019; 2019

Stress has become a partof our lives; evidence show that chronic stress exposure during pregnancy canhave long lasting effects on the developing fetal brain. Therefore,understanding how the stress signal is transmitted from mother to child can helpdetect stress effects on early stages and prevent disease onset. Theglycoprotein M6a is a stress responsive protein that is coupled toextracellular vesicles (EVs) in serum. After stress, M6a levels on serum EVsmirrored M6a hippocampal changes suggesting that brain information can be readin peripheral fluids. ObjectiveTo analyzestress molecules transference between mother and fetus and vice versaMethodsPregnant C57Bl/6J dams are submitted to a variablestress paradigm from GD8 to GD17 (PS group) or left undisturbed (C group). Damsare sacrificed on GD18. We collect maternal blood and hippocampus, placenta,amniotic fluid and fetal hippocampus. EVs are isolated by centrifugation frommaternal serum and amniotic fluid. Fetal EVs are captured from maternalcirculation with contactin-2 antibody. EVs integrity and morphology are assayedby TEM microscopy. Classical EV markers and stress genes expression (identifiedby proteomic analysis) on EVs from PS and C groups are tested by Western blot. Transference of moleculesfrom mother to fetus via EVs will be studied by in utero electroporation using M6a-GFP plasmid and then detectingGFP on fetal EVs. ResultsWe found increased M6a levels in the maternal brainand placentas of PS group compared to C dams. Interestingly, amniotic fluid andfetal hippocampus showed reduced M6a levels. Our ongoing work will determine ifcirculating EVs from PS and C groups carry different molecules and ifevaluation of fetal status can be done by analyzing fetal EVs isolated frommaternal circulation.ConclusionsThe study of the circulating EVs liberated by thestressed mother and/or fetus could shed light into relevant molecules, such as M6a,that could be used as early markers of stress.