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.