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Article Dans Une Revue Toxicology Letters Année : 2016

Multigenerational effects of chronic low-dose natural uranium contamination: Epigenetic inheritance of methylation signature

Résumé

Introduction: In industrialized countries the high prevalence and incidence of certain diseases are important topics to social and media actuality. Scientific data suggest that the gradual deterioration in the quality of our environment may be due to pollution, the increasing use of radioelements, especially nuclear power plants. The health consequences of epigenetic alterations and its heritability, caused by the chronic ingestion of radionuclides, remain unknown. That creates concerns regarding the effects of chronic low dose environmental contamination. Indeed, recently, a paradigm shift in the perception of risk of radiotoxicology has emerged. It is now investigated the possibility of transmission of biological effects over generations, in particular by epigenetic pathways. These processes are known for their crucial role associated to the development of several diseases. Objective: Our hypothesis is that exposure to a chronic lowdoses of radionuclides, such as uranium, could affect the epigenetic profile and, therefore, could be transmitted across generations. Materials and methods: The first generation (F0) of male and female rats was contaminated during 9 months via drinking water using a non-toxic concentration (40mgL−1) of natural uranium. The second generation F1 was exposed only until weaning. The third generation (F2) was not exposed to uranium. The uranium effects on DNA were evaluated on the three generations by analyzing the DNA methylation profile and DNMT genes expression in the ovaries and in the testes. Results: Here we report a significant hypermethylation (F0 17%, F1 41% and F2 42%) of testes DNA (p < 0.005). However, ovaries DNA was hypomethylated (F0 18%, F1 41% and F2 21%) (p < 0.005). Interestingly, this DNA methylation profile was significantly maintained across generations. Quantitative RT-PCR demonstrates a modification in DNA methyltransferase genes (DNMT 1, DNMT3a/b and DNMT3L). Conclusion: All in all, our work demonstrates for the first time, that the outcome of the exposition to low doses of uranium on male and female rats was significantly different. This suggests that methylation changes are sex- and tissue-dependent mechanisms. Therefore, our results indicate the involvement of an epigenetic mechanism as a biological response to the exposure to chronic low doses of uranium. The biological significance of these results and which are the uranium effects on reproductive cells is still to be answered.
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Dates et versions

hal-03820726 , version 1 (19-10-2022)

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G. Elmhiri, C. Gloaguen, D. Kereselidze, S. Grison, A. Legendre, et al.. Multigenerational effects of chronic low-dose natural uranium contamination: Epigenetic inheritance of methylation signature. Toxicology Letters, 2016, 259, pp.S114. ⟨10.1016/j.toxlet.2016.07.293⟩. ⟨hal-03820726⟩

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