Benzo(a)pyrene and Cerium Dioxide Nanoparticles in Co-Exposure Impair Human Trophoblast Cell Stress Signaling
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Published:2023-03-12
Issue:6
Volume:24
Page:5439
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Deval Gaëlle1ORCID, Nedder Margaux1, Degrelle Séverine2ORCID, Rogozarski Jasmina1, Vignaud Marie-Léone1ORCID, Chissey Audrey1, Colzin Stacy1, Laguillier-Morizot Christelle13ORCID, Coumoul Xavier4ORCID, Boland Sonja5, Fournier Thierry1ORCID, Zerrad-Saadi Amal1ORCID, Ferecatu Ioana1ORCID
Affiliation:
1. Université Paris Cité, Inserm, 3PHM, F-75006 Paris, France 2. Inovarion, F-75005 Paris, France 3. Hormonology Department, Cochin Hospital, AP-HP, F-75014 Paris, France 4. Université Paris Cité, Inserm, UMR-S 1124, F-75006 Paris, France 5. Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, F-75013 Paris, France
Abstract
Human placenta is a multifunctional interface between maternal and fetal blood. Studying the impact of pollutants on this organ is crucial because many xenobiotics in maternal blood can accumulate in placental cells or pass into the fetal circulation. Benzo(a)pyrene (BaP) and cerium dioxide nanoparticles (CeO2 NP), which share the same emission sources, are found in ambient air pollution and also in maternal blood. The aim of the study was to depict the main signaling pathways modulated after exposure to BaP or CeO2 NP vs. co-exposure on both chorionic villi explants and villous cytotrophoblasts isolated from human term placenta. At nontoxic doses of pollutants, BaP is bioactivated by AhR xenobiotic metabolizing enzymes, leading to DNA damage with an increase in γ-H2AX, the stabilization of stress transcription factor p53, and the induction of its target p21. These effects are reproduced in co-exposure with CeO2 NP, except for the increase in γ-H2AX, which suggests a modulation of the genotoxic effect of BaP by CeO2 NP. Moreover, CeO2 NP in individual and co-exposure lead to a decrease in Prx-SO3, suggesting an antioxidant effect. This study is the first to identify the signaling pathways modulated after co-exposure to these two pollutants, which are common in the environment.
Funder
ANR JCJC ANSES French Ministry of Research French National Institute of Health and Medical Research Université Paris Cité
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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