Cerium dioxide nanoparticles affectin vitrofertilization 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.

Cerium Oxide Nanoparticles in Lung Acutely Induce Oxidative Stress, Inflammation, and DNA Damage in Various Organs of Mice

“…Moreover, it has been shown that CeO 2 NPs induce oxidative stress and genotoxicity in human skin melanoma cells and human dermal fibroblasts [59, 60]. A more recent study has shown that low and more relevant concentration of CeO 2 NPs (0.01 mg/L) adversely affected in vitro fertilization in mice and caused DNA damage in mouse spermatozoa and oocytes [61]. The observed DNA damage was explained by the direct impact of CeO 2 NPs and/or mechanical impact on the disruption of gamete interactions.…”

“…In fact, the same research group has demonstrated earlier the accumulation of CeO 2 NPs along oocyte zona pellucida [62]. Finally, it has also been suggested that CeO 2 NPs could negatively impact fertilization by causing oxidative stress [61]. …”

SERENADE: safer and ecodesign research and education applied to nanomaterial development, the new generation of materials safer by design

“…During in vitro fertilization of mouse 1272 oocytes, we showed a significant decrease of fertilization rate, at a very low concentration (0.01 mg L −1 ) of CeO 2 NPs. We also showed significant DNA damage induced in vitro by CeO 2 NPs on mouse spermatozoa and oocytes at the same low concentration [37][38][39] using the Comet assay. As an orthogonal method, we used transmission electron microscopy to determine the location of accumulation of the particles within or outside the cells.…”

Towards a New Paradigm in Nano‐Genotoxicology: Facing Complexity of Nanomaterials’ Cellular Interactions and Effects

“…It was recently shown that serum proteins form a corona and can modulate genotoxicity of NMs . Hence, not only ROS production but also direct binding to/physical disruption of membranes or proteins such as tubulins and/or actins , altered protein conformation, RNA binding , mechanical stress leading to changes in downstream cellular signalling pathways may be at work to induce genotoxicity, therefore suggesting new MoA.…”