Effets biologiques des nanoparticules de cérium enrobées de benzo-[a]-pyrène sur la barrière placentaire humaine
Résumé
The placenta is a multifunctional organ essential for fetal growth and pregnancy outcome, who represents a barrier to protect the fetus from exposure to xenobiotics. Benzo-(a)-pyrene (BaP) is already known to be a mutagenic and reprotoxic carcinogen as well as an endocrine disruptor, which can cross the placental barrier. Cerium dioxide nanoparticles (CeO2 NPs) are a more recent pollutant sharing the same emission sources as BaP (cigarette smoke, diesel engine exhaust gases). Objective: The aim of our study was to determine the mechanisms of action of these two air pollutants on the placental barrier, when they are in co-exposure, as most representative of the environmental reality. The ratio of concentrations chosen is of 6.3 µg / cm2 of CeO2 NPs for 0.6 µM of BaP, which corresponds to the quantity of BaP sufficient to cover the NP surface. These concentrations are not cytotoxic for the placenta but disturb its functioning. Methods: A Cell Stress Array was performed in order to identify the signaling pathways modulated after exposure to these two pollutants on villous cytotrophoblasts isolated from human term placentas. The results obtained were confirmed by Western blot. Results: We showed that BaP activates AhR signaling pathway, stabilizes p53 and its transcriptional target p21 without changes in antioxidant enzymes levels. On the contrary, CeO2 NPs have an antioxidant effect and decrease the level of factors such as HIF-1, HIF-2, p38 and NFB, as well as their signaling pathways. These effects are potentiated after co-exposure to both pollutants. Conclusions: The Cell Stress Array highlights a greater number of actors, whose protein levels decrease in co-exposure compared to individual exposures, suggesting synergic signaling modulation in relation to individual expositions. These results open up new perspectives to depict the mechanisms by which these two air pollutants impair placenta functioning of exposed pregnant women.
