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Multigenerational effects of chronic low-dose natural uranium contamination: Epigenetic inheritance of methylation signature
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International audience. Introduction: In industrialized countries the high prevalenceand incidence of certain diseases are important topics to social and media actuality. Scientific data suggest that the gradual deteriorationin the quality of our environment may be due to pollution,the increasing use of radioelements, especially nuclear powerplants. The health consequences of epigenetic alterations andits heritability, caused by the chronic ingestion of radionuclides,remain unknown. That creates concerns regarding the effects ofchronic low dose environmental contamination. Indeed, recently,a paradigm shift in the perception of risk of radiotoxicology hasemerged. It is now investigated the possibility of transmission ofbiological effects over generations, in particular by epigenetic pathways.These processes are known for their crucial role associatedto the development of several diseases.Objective: Our hypothesis is that exposure to a chronic lowdosesof radionuclides, such as uranium, could affect the epigeneticprofile and, therefore, could be transmitted across generations.Materials and methods: The first generation (F0) of male andfemale rats was contaminated during 9 months via drinking waterusing a non-toxic concentration (40mgL−1) of natural uranium.The second generation F1 was exposed only until weaning. Thethird generation (F2) was not exposed to uranium. The uraniumeffects on DNA were evaluated on the three generations by analyzingthe DNA methylation profile and DNMT genes expression in theovaries 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 DNAwas hypomethylated (F0 18%, F1 41% and F2 21%) (p < 0.005). Interestingly,this DNA methylation profile was significantly maintainedacross generations. Quantitative RT-PCR demonstrates a modificationin DNA methyltransferase genes (DNMT 1, DNMT3a/b andDNMT3L).Conclusion: All in all, our work demonstrates for the first time,that the outcome of the exposition to low doses of uranium onmale and female rats was significantly different. This suggests thatmethylation changes are sex- and tissue-dependent mechanisms.Therefore, our results indicate the involvement of an epigeneticmechanism as a biological response to the exposure to chronic lowdoses of uranium. The biological significance of these results andwhich are the uranium effects on reproductive cells is still to beanswered.
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