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

International audienceIntroduction: 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

Low dose of uranium induces multigenerational epigenetic effects in rat kidney

International audiencePurpose A protocol of chronic exposure to low dose of uranium was established in order to distinguish the sexual differences and the developmental process that are critical windows for epigenetic effects over generations. Methods Both male and female rats were contaminated through their drinking water with a non-toxic solution of uranyl nitrate for 9 months. The exposed generation (F0) and the following two generations (F1 and F2) were examined. Clinical monitoring, global DNA methylation profile and DNA methyltransferases (DNMTs) gene expression were analyzed in kidneys. Results While the body weight of F1 males increased, a small decrease in kidney and body weight was observed in F2 males. In addition, global DNA hypermethylation profile in kidney cells was observed in F1 and F2 males. qPCR results reveal a significant increase of methyltransferase genes expression (DNMT1 and DNMT3a) for F2 females. Conclusions In the field of public health policy and to raise attention to generational effects for the risk assessment of the environmental exposures, low doses of uranium do not imply clinical effects on adult exposed rats. However, our results confirm the importance of the developmental windows’ sensitivity in addition to the sexual dimorphisms of the offspring. © 2018, Copyright © 2018 Taylor and Francis Group LLC