title: Cerium dioxide nanoparticles affect in vitro fertilization in mice.
abstract: Due to their catalytic and oxidative properties, cerium dioxide nanoparticles (CeO2NPs) are widely used as diesel additive or as promising therapy in cancerology; yet, scarce data are available on their toxicity, and none on their reproductive toxicity. We showed a significant decrease of fertilization rate, assessed on 1272 oocytes, during in vitro fertilization (IVF) carried out in culture medium containing CeO2NP at very low concentration (0.01 mg.l(-1)). We also showed significant DNA damage induced in vitro by CeO2NP on mouse spermatozoa and oocytes at 0.01 mg.l(-1) using Comet assay. Transmission Electron Microscopy did not detect any nanoparticles in the IVF samples at 0.01 mg.l(-1), but showed, at high concentration (100 mg.l(-1)), their endocytosis by the cumulus cells surrounding oocytes and their accumulation along spermatozoa plasma membranes and oocytes zona pellucida. We did not observe any nanoparticles in the cytoplasm of spermatozoa, oocytes or embryos. This study demonstrates for the first time the impact of CeO2NP on in vitro fertilization, as well as their genotoxicity on mouse spermatozoa and oocytes, at low nanoparticle concentration exposure. Decreased fertilization rates may result from: (1) CeO2NP's genotoxicity on gametes; (2) a mechanical effect, disrupting gamete interaction and (3) oxidative stress induced by CeO2NP. These results add new and important insights with regard to the reproductive toxicity of nanomaterials requesting urgent evaluation, and support several publications on metal nanoparticles reprotoxicity. Our data highlight the need for in vivo studies after low-dose exposure.
authors.affiliation: a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .
authors.forename: Lise
authors.initials: L
authors.lastname: Preaubert
authors.affiliation: a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .|b Pôle de Gynécologie-Obstétrique et Reproduction, Gynepole, AP-HM, Hôpital de La Conception , 147 Bd Baille , 13 385 Marseille Cedex 05 , France .
authors.forename: Blandine
authors.initials: B
authors.lastname: Courbiere
authors.affiliation: a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .|c CECOS Laboratory Biology of Reproduction, AP-HM Gynepole , Marseille Cedex , France , and.
authors.forename: Vincent
authors.initials: V
authors.lastname: Achard
authors.affiliation: a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .
authors.forename: Virginie
authors.initials: V
authors.lastname: Tassistro
authors.affiliation: a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .
authors.forename: Fanny
authors.initials: F
authors.lastname: Greco
authors.affiliation: a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .
authors.forename: Thierry
authors.initials: T
authors.lastname: Orsiere
authors.affiliation: d CEREGE UMR 7330, CNRS; Aix-Marseille Université- IRD; Technopole de l'Arbois BP 80 , 13545 Aix en Provence , France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Bottero
authors.affiliation: d CEREGE UMR 7330, CNRS; Aix-Marseille Université- IRD; Technopole de l'Arbois BP 80 , 13545 Aix en Provence , France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Rose
authors.affiliation: d CEREGE UMR 7330, CNRS; Aix-Marseille Université- IRD; Technopole de l'Arbois BP 80 , 13545 Aix en Provence , France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Auffan
authors.affiliation: a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .|c CECOS Laboratory Biology of Reproduction, AP-HM Gynepole , Marseille Cedex , France , and.|d CEREGE UMR 7330, CNRS; Aix-Marseille Université- IRD; Technopole de l'Arbois BP 80 , 13545 Aix en Provence , France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Perrin
mesh_terms: D000818:Animals; D002563:Cerium / Q000633:toxicity*; D004249:DNA Damage; D005260:Female; D005307:Fertilization in Vitro; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D009865:Oocytes / Q000187:drug effects; D018384:Oxidative Stress; D013094:Spermatozoa / Q000187:drug effects
chemical_list: D002563:Cerium; C030583:ceric oxide
keywords: Comet assay; DNA damage; mouse spermatozoa; oocyte; reproductive toxicity