title: Pulmonary exposure to metallic nanomaterials during pregnancy irreversibly impairs lung development of the offspring.
abstract: Due to the growing commercial applications of manufactured nanoparticles (NPs), toxicological studies on NPs, especially during the critical window of development, are of major importance. The aim of the study was to assess the impact of respiratory exposure to metallic and metal oxide NPs during pregnancy on lung development of the offspring and to determine the key parameters involved in lung alterations. Pregnant mice were exposed to weekly doses of 100 μg (total dose 300 μg) of titanium dioxide (TiO2), cerium oxide (CeO2), silver (Ag) NPs or saline solution by nonsurgical intratracheal instillation. The offspring lungs were analyzed at different stages of lung development: fetal stage (gestational day 17.5), pulmonary alveolarization (post-delivery day 14.5) and lung maturity (post-delivery day 49.5). Regardless of the type of NP, maternal exposure during gestation induced long-lasting impairment of lung development of the offspring. This effect was accompanied by: i) decreased placental efficiency together with the presence of NPs in placenta, ii) no increase of inflammatory mediators present in amniotic fluid, placenta or offspring lungs and iii) decreased pulmonary expression of vascular endothelial growth factor-α (VEGF-α) and matrix metalloproteinase 9 (MMP-9) at the fetal stage, and fibroblast growth factor-18 (FGF-18) at the alveolarization stage. Respiratory exposure to metallic NPs during pregnancy induces stereotyped impairment of lung development with a lasting effect in adult mice, independently of the chemical nature of the NP.
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Paul
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Franco-Montoya
authors.affiliation: c Laboratoire de Physique des Solides, CNRS, University of Paris-Sud, Université Paris-Saclay , Orsay , France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Paineau
authors.affiliation: d CEREGE, Aix Marseille Université-CNRS-IRD-Collège de France , Aix-en-Provence , France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Angeletti
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Shamila
authors.initials: S
authors.lastname: Vibhushan
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Ridoux
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Tiendrebeogo
authors.affiliation: e European Synchrotron Radiation Facility , Grenoble , France.
authors.forename: Murielle
authors.initials: M
authors.lastname: Salome
authors.affiliation: e European Synchrotron Radiation Facility , Grenoble , France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hesse
authors.affiliation: f Synchrotron SOLEIL , Gif-sur-Yvette , France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Vantelon
authors.affiliation: d CEREGE, Aix Marseille Université-CNRS-IRD-Collège de France , Aix-en-Provence , France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rose
authors.affiliation: g DHU A-TVB, IMRB, EA 7376 CEpiA (Clinical Epidemiology And Ageing Unit) , Université Paris-Est Créteil (UPEC) , Créteil , France.|h Public Health Department , AP-HP, Henri-Mondor Teaching Hospital , Créteil , France.
authors.forename: Florence
authors.initials: F
authors.lastname: Canouï-Poitrine
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanone
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Delacourt
authors.affiliation: a Inserm U955, Equipe 04 , Créteil , France.|b Faculté de Médecine, DHU A-TVB, IMRB , Université Paris Est Créteil , Créteil , France.|i Centre Hospitalier Intercommunal, Institut Santé-Travail Paris-Est , Créteil , France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pairon
mesh_terms: D000393:Air Pollutants / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D002563:Cerium / Q000633:toxicity; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D038081:Organogenesis / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012834:Silver / Q000378:metabolism; D014025:Titanium / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D042461:Vascular Endothelial Growth Factor A; C113569:fibroblast growth factor 18; C009495:titanium dioxide; D002563:Cerium; D012834:Silver; C030583:ceric oxide; D005346:Fibroblast Growth Factors; D014025:Titanium
keywords: Nanoparticles; lung development; pregnancy; toxicology