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.

• Comet assay
• DNA damage
• mouse spermatozoa
• oocyte
• reproductive toxicity

Acknowledgements

We thank Joel Courageot for expert preparation and analysis of TEM samples, Amandine Sansoni and Fabien Danjean for advises and training for mouse IVF, Armand Tasmadjian and Michael Mitchell for technical help to achieve this project, and the Centre de Formation et de Recherches Experimentales Medico-Chirurgicales, Aix-Marseille University, for care and counseling concerning laboratory mice.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

This work is a contribution to the Labex Serenade (n° ANR-11-LABX-0064) funded by the “Investissements d’Avenir” French Government program of the National Research Agency through the A*MIDEX project (n° ANR-11-IDEX-0001-02).

Supplementary material available online

Supplementary Figures S1-S2.