title: Ultrastructural interactions and genotoxicity assay of cerium dioxide nanoparticles on mouse oocytes.
abstract: Cerium dioxide nanoparticles (C(e)O₂ ENPs) are on the priority list of nanomaterials requiring evaluation. We performed in vitro assays on mature mouse oocytes incubated with C(e)O₂ ENPs to study (1) physicochemical biotransformation of ENPs in culture medium; (2) ultrastructural interactions with follicular cells and oocytes using Transmission Electron Microscopy (TEM); (3) genotoxicity of C(e)O₂ ENPs on follicular cells and oocytes using a comet assay. DNA damage was quantified as Olive Tail Moment. We show that ENPs aggregated, but their crystal structure remained stable in culture medium. TEM showed endocytosis of C(e)O₂ ENP aggregates in follicular cells. In oocytes, C(e)O₂ ENP aggregates were only observed around the zona pellucida (ZP). The comet assay revealed significant DNA damage in follicular cells. In oocytes, the comet assay showed a dose-related increase in DNA damage and a significant increase only at the highest concentrations. DNA damage decreased significantly both in follicular cells and in oocytes when an anti-oxidant agent was added in the culture medium. We hypothesise that at low concentrations of C(e)O₂ ENPs oocytes could be protected against indirect oxidative stress due to a double defence system composed of follicular cells and ZP.
authors.affiliation: Institut Méditerranéen de Biodiversité et d'Ecologie marine et continentale (IMBE), Biogénotoxicologie-Santé humaine et environnement (UMR CNRS 7263-FR CNRS 3098), Aix-Marseille Université, Faculté de médecine, 27 Bd Jean Moulin, Marseille 13005, France. blandine.courbiere@ap-hm.fr.
authors.forename: Blandine
authors.initials: B
authors.lastname: Courbiere
authors.forename: Mélanie
authors.initials: M
authors.lastname: Auffan
authors.forename: Raphaël
authors.initials: R
authors.lastname: Rollais
authors.forename: Virginie
authors.initials: V
authors.lastname: Tassistro
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bonnefoy
authors.forename: Alain
authors.initials: A
authors.lastname: Botta
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rose
authors.forename: Thierry
authors.initials: T
authors.lastname: Orsière
authors.forename: Jeanne
authors.initials: J
authors.lastname: Perrin
mesh_terms: D000818:Animals; D002563:Cerium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004249:DNA Damage; D005260:Female; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D009152:Mutagenicity Tests; D009865:Oocytes / Q000187:drug effects* / Q000648:ultrastructure; D006080:Ovarian Follicle / Q000187:drug effects* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D015044:Zona Pellucida / Q000648:ultrastructure
chemical_list: D002563:Cerium; C030583:ceric oxide