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Cerium dioxide nanoparticles affect in vitro fertilization in mice
Lise Preaubert1, Blandine Courbiere1,2, Vincent Achard1,3
1a Aix Marseille Université, CNRS, IRD, Avignon Université, IMBE UMR 7263 , 13397, Marseille , France .
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.
Insights
Cerium dioxide nanoparticles (CeO2NPs) significantly reduced fertilization rates and caused DNA damage in mouse gametes during in vitro fertilization. These findings highlight the reproductive toxicity of CeO2NPs, necessitating further in vivo studies.
Area of Science:
- Nanotechnology
- Reproductive Toxicology
- Environmental Health
Background:
- Cerium dioxide nanoparticles (CeO2NPs) possess catalytic and oxidative properties, leading to widespread use in diesel additives and cancer therapy.
- Limited data exists on CeO2NP toxicity, with no available information on their reproductive effects.
Purpose of the Study:
- To investigate the impact of CeO2NPs on in vitro fertilization (IVF) and assess their genotoxicity on mouse spermatozoa and oocytes.
- To determine the potential reproductive risks associated with low-dose exposure to CeO2NPs.
Main Methods:
- In vitro fertilization (IVF) assays were performed using mouse oocytes exposed to varying concentrations of CeO2NPs.
- Comet assay was employed to evaluate DNA damage in spermatozoa and oocytes.
- Transmission Electron Microscopy (TEM) was used to visualize nanoparticle uptake and localization.
Main Results:
- A significant decrease in fertilization rate was observed at a low CeO2NP concentration (0.01 mg.l⁻¹).
- Significant DNA damage was induced in mouse spermatozoa and oocytes by CeO2NPs at 0.01 mg.l⁻¹.
- TEM revealed nanoparticle endocytosis by cumulus cells and accumulation on gamete surfaces at high concentrations, but not within gamete cytoplasm.
Conclusions:
- CeO2NPs negatively impact in vitro fertilization and exhibit genotoxicity towards mouse spermatozoa and oocytes, even at low concentrations.
- Potential mechanisms for decreased fertilization include gamete genotoxicity, mechanical disruption, and oxidative stress induced by CeO2NPs.
- These findings underscore the reproductive toxicity of nanomaterials and the urgent need for comprehensive in vivo risk assessments.
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