Stéphane Grison will defend his thesis
on Thursay 13th December 2018 at 2:00 pm
at IRSN, in the auditorium (building 01)
31 avenue de la Division Leclerc
Pr Anne-Marie Lefrançois-Martinez (UCA), President
Pr Francelyne Marano (Université Paris-Diderot), reporter
Pr Zdenko Herzeg (IARC, Lyon), reporter
Dr Isabelle Dublineau (IRSN), examiner
Dr Jean-Charles Martin (AMU), invited member
Dr Éric Bonner (CNG), invited member
Dr Maâmar Souidi (IRSN), thesis Supervisor
Pr Jean-Marc Lobaccaro (UCA), thesis Supervisor
In order to deepen scientific knowledge regarding biological effects of radionuclides and associated risk to offspring, an in vivo multigenerational study of chronic exposure to a nontoxic dose of uranium was performed by monitoring three generation of rats (F0, F1 and F2). Clinical parameters and biological markers, including metabolomics, transcriptomics and epigenomics high throughput analysis were conducted in blood, urine and kidney samples.
For the first generation of contaminated rats (F0) sex-differences to uranium effects were observed in kidney for gene expression (mRNA, miRNA) and in kidney, urine and blood for biochemical parameters and metabolomics profiles. No epigenetic modification of DNA methylation profiles was shown in kidney. For the next two generations (F1, F2), a multigenerational sex-specific effect is observed for both metabolomics and renal DNA methylation profiles of contaminated rats. Moreover, for the last generation of male rats (F2), a decrease of both total body and kidney weight was shown.
In conclusion, low-dose chronic contamination of rats to uranium leads to multigenerational effects. Including sex-differences, they can be shown at different molecular levels of the cellular system. Depending of integrated system biology, data of this thesis are useful in the understanding of biological mechanisms of uranium effect and risk of delayed harmful effect. In the field of radiation protection, these results prove the requirement of considering sexual dimorphisms and consequences of such exposures to offspring.