Pulmonary exposure to metallic nanomaterials during pregnancy irreversibly impairs lung development of the offspring

• Published in: Nanotoxicology Vol. 11; no. 4; pp. 484 - 495
• Main Authors: Paul, Emmanuel, Franco-Montoya, Marie-Laure, Paineau, Erwan, Angeletti, Bernard, Vibhushan, Shamila, Ridoux, Audrey, Tiendrebeogo, Arnaud, Salome, Murielle, Hesse, Bernhard, Vantelon, Delphine, Rose, Jérôme, Canouï-Poitrine, Florence, Boczkowski, Jorge, Lanone, Sophie, Delacourt, Christophe, Pairon, Jean-Claude
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 21.04.2017; Taylor & Francis Ltd
• Subjects: Air Pollutants - pharmacokinetics; Air Pollutants - toxicity; Amniotic fluid; Animals; Biocompatibility; Cerium; Cerium - toxicity; Cerium oxides; Developmental stages; Dioxides; Efficiency; Exposure; Female; Fetuses; Fibroblast growth factor 18; Fibroblast Growth Factors - metabolism; Gelatinase B; Gestation; Growth factors; Human health and pathology; Impairment; Inflammation; Inhalation Exposure - adverse effects; Life Sciences; Lung - drug effects; Lung - embryology; Lung - metabolism; lung development; Lungs; Male; Maternal Exposure - adverse effects; Matrix metalloproteinase; Maturity; Metal Nanoparticles - toxicity; Metalloproteinase; Metals; Mice; Mice, Inbred C57BL; Nanomaterials; Nanoparticles; Nanotechnology; Offspring; Organogenesis - drug effects; Placenta; Placenta - drug effects; Placenta - metabolism; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Pulmonology and respiratory tract; Rodents; Saline solutions; Silver; Silver - metabolism; Surgical implants; Titanium - toxicity; Titanium dioxide; Toxicity testing; toxicology; Trachea; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Nanoparticles; toxicology; lung development; pregnancy
• DOI: 10.1080/17435390.2017.1311381
• ISSN: 1743-5390

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 (TiO 2 ), cerium oxide (CeO 2 ), 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.