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Environnement, Risques & Santé

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From metabolome to epigenome: example of multiscale analysis for studying the effects of low-dose uranium exposure Volume 19, issue 5, September-October 2020

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Authors
Institut de radioprotection et de sûreté nucléaire
PSE-SANTE
F 92262 Fontenay-aux-Roses Cedex
France
* Tirés à part

This study developed an in vivo protocol of chronic uranium exposure to examine the biological effects of these chronic exposures to the low doses to which human populations may be exposed; it used omics analysis as well as conventional clinical monitoring. Metabolomics analysis revealed an observable sexual dimorphism in the kidneys, urine, and blood plasma of exposed animals. It also showed that the metabolisms most strongly affected were those of nicotinate-nicotinamide and of unsaturated fatty acid biosynthesis. Upstream of the metabolism, transcriptomic analyses of the kidney revealed genetic and epigenetic responses to uranium. At the epigenetic level, analysis of kidney DNA methylation revealed that this methylation increased for two generations of males born to a female exposed while pregnant (while DNA methylation of female offspring kidneys was not affected). A multiscale analysis of the metabolomic and transcriptomic findings showed new molecular pathways associated with uranium exposure. These multiscale analyses could be relevant for decrypting the biological mechanisms of low-dose exposures. Finally, these results highlight the importance of gender in estimating sensitivity to low-dose exposure and draw attention to the need to take this component into account in risk assessment.