Maternal‐fetal communication of stressful signals via extracellular vesicles

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

Congreso; International Federation of Placenta Associations 2019 (IFPA2019); 2019

Maternal-fetal communication of stressfulsignals via extracellular vesicles Melisa C. Monteleone, Silvia C. Billi,Eliana M. Fernández and Marcela A. Brocco.Instituto deInvestigaciones Biotecnológicas. UNSAM. CONICET. San Martín, BuenosAires. Argentina. mmonteleone@iibintech.com.ar Objective: Evidence show that chronic stressexposure during pregnancy may affect the developing fetal brain increasingdisease risk. Therefore, finding stress signals that are transmitted frommother to child can help detect stress effects on early stages and preventdisease onset. A candidate stress signal is the neuronal glycoprotein M6a,which levels are altered in the brain of prenatally stressed offspring.Moreover, after stress, serum M6a levels mirror brain changes suggesting thatbrain information can be read in peripheral fluids. Interestingly, incerebrospinal fluid and serum, M6a circulates coupled to extracellular vesicles(EVs).Wehypothesize that maternal EVs carrying M6a could travel or accumulate inplacenta as a mean to transmit stress to the fetus. We sought to analyze thetransference of EV-associated stress molecule between mother and fetus.Methods: Pregnant C57Bl/6J dams were subjectedto a variable stress paradigm from gestational day (GD) 8 to GD17 (PS group) orleft undisturbed (C group). Dams were sacrificed on GD18. Maternal blood andhippocampi, placenta, amniotic fluid and fetal hippocampi were collected. M6aexpression from PS and C groups was tested by Western blot.Results: Compared to control dams, we found inthe maternal brain and placentas of PS group increased M6a levels.Interestingly, in comparison to control, PS amniotic fluid and fetalhippocampus showed reduced M6a levels. Since M6a is coupled to EVs, our ongoingwork will determine if maternal circulating EVs from PS and C groups carrydifferent molecules.Conclusions:  Differences between control andstressed individuals suggest that M6a per se or molecules co-transported withit could be one way to transmit stress signal to fetus. Such molecules could beused as early markers of stress.