Low dose of uranium induces multigenerational epigenetic effects in rat kidney

Grison, Stéphane; Elmhiri, Ghada; Gloaguen, C.; Elie, Christelle; Kereselidze, Dimitri; Tack, Karine; Lestaevel, Philippe; Legendre, Audrey; Manens, Line; Benadjaoud, Mohamed Amine; Lobaccaro, Jean-Marc A.; Souidi, Maâmar

doi:10.1080/09553002.2018.1493242

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…To address this question, a protocol to study the multigenerational effects of chronic exposure to low doses of uranium was developed in rats. In this study, the overall DNA methylation levels in the rats’ kidneys (males and females) were analysed over three generations of rats: (F0) contaminated for 9 months from birth, (F1) contaminated in utero and then until weaning and potentially affected by the paternal (F0) germ cells and, lastly, (F2) only potentially affected via the germ cells of their parents (F1) [ 59 ] ( Fig. 2 ).…”

Section: Methods Results and Discussionmentioning

confidence: 99%

Use of omics analysis for low-dose radiotoxicology and health risk assessment: the case of uranium

Grison

Souidi

2022

Environmental Epigenetics

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Exposure to environmental pollution and the increase in incidence of multifactorial diseases in the population have become health problems for industrialized countries. In this context, the question of the health impact of exposure to these pollutants is not clearly identified in the low dose range. This article looks at this problem using the example of preclinical studies of the effects of chronic low-dose exposure to uranium in rats. These studies demonstrate the value of molecular screening analyses (omics) and multimodal integrative approaches, of which the extreme sensitivity and breadth of observation spectrum make it possible to observe all the biological processes affected and the mechanisms of action triggered at molecular level by exposure to low doses. They also show the value of these analytical approaches for finding diagnostic biomarkers or indicators of prognosis, which can be necessary to evaluate a risk. Finally, the results of these studies raise the question of the health risk caused by epigenomic deregulations occurring during critical developmental phases and their potential contribution to the development of chronic diseases that are metabolic in origin or to the development of certain cancer liable in the long term to affect the exposed adult and possibly its progeny.

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Section: Methods Results and Discussionmentioning

confidence: 99%

Use of omics analysis for low-dose radiotoxicology and health risk assessment: the case of uranium

Grison

Souidi

2022

Environmental Epigenetics

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“…Regarding the risk of heritable effects of such exposure, recent studies have shown differences in global DNA methylation levels in the gonads of exposed individuals at different developmental stages, but also in other organs such as the kidneys [ 12 , 43 ]. These result show, on the one hand, that chronic exposure to low doses of NU can modify the DNA methylation profile of kidney cells (main toxicological target of uranium), but also that uranium could have a genetic effect on the gonads of adult males, even if they are only exposed during the embryonic and fetal periods of generation F0 and the germinal period for the animals in generation F1.…”

Section: Discussionmentioning

confidence: 99%

“…The multigenerational study design is already described in [ 12 , 43 ] ( Figure 6 ). In summary, the present protocol includes three generations (F0, F1 and F2) of male and female rats (n = 20).…”

Section: Methodsmentioning

confidence: 99%

Multigenerational Exposure to Uranium Changes Sperm Metabolome in Rats

Grison

Legendre

Svilar

et al. 2022

IJMS

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Male infertility is a major public health issue that can be induced by a host of lifestyle risk factors such as environment, nutrition, smoking, stress, and endocrine disruptors. Regarding the human population exposed to uranium, it is necessary to explore these effects on male reproduction in multigenerational studies. The sensitivity of mass spectrometry (MS)-based methods has already proved to be extremely useful in metabolite identification in rats exposed to low doses of uranium, but also in human sperm. We applied this method to rat sperm over three generations (F0, F1 and F2) with multigenerational uranium exposure. Our results show a significant content of uranium in generation F0, and a reduction in the pregnancy rate only in generation F1. Based on principal component analysis (PCA), we observed discriminant profiles between generations. The partial least squares discriminant analysis (PLS-DA) of the 48 annotated variables confirmed that parental exposure of generation F0 (during both the preconceptional and prenatal periods) can have metabolic effects on spermatozoa for the next two generations. Metabolomics applied to epididymal spermatozoa is a novel approach to detecting the multigenerational effects of uranium in an experimental model, but could be also recommended to identify potential biomarkers evaluating the impact of uranium on sperm in exposed infertile men.

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“…Néanmoins, aucune des solutions n'était suffisamment concentrée pour être toxique chez le via les cellules germinales de la génération précédente exposée (F1) [52] (Figure 3).…”

Section: Effet Du Temps Effet De La Doseunclassified

“…Pour la seconde génération (F2) une légère baisse de la masse corporelle accompagnée d'une diminution de la masse des reins, ont été observées exclusivement chez les animaux mâles (les femelles ne présentant toujours pas de différences significatives notables). De même, une hyperméthylation de l'ADN a aussi été observée au niveau des reins mâles de la première génération (F1) et de la seconde génération (F2) descendants de la génération F0 des parents contaminés à l'uranium [52].…”

Section: Effet Du Temps Effet De La Doseunclassified

From metabolome to epigenome: example of multiscale analysis for studying the effects of low-dose uranium exposure

Grison¹,

Souidi²

2020

Environnement Risques Santé

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Pour étudier les effets biologiques des expositions chroniques à faibles doses d'uranium auxquelles les populations humaines peuvent être exposées, un protocole in vivo d'exposition chronique à l'uranium de rats (mâles et femelles) a été élaboré et des analyses omiques ont été réalisées en complément d'un suivi clinique classique. Les analyses métabolomiques ont révélé l'existence d'un dimorphisme sexuel observable au niveau des reins, des urines et du plasma chez les animaux contaminés. Elles ont aussi montré que les métabolismes les plus affectés par l'uranium étaient ceux du nicotinate-nicotinamide et de la biosynthèse des acides gras insaturés. Plus en amont, l'analyse du transcriptome des reins a aussi permis de mettre en évidence des effets géniques et épigénétiques de l'uranium. Au niveau épigénétique, une hyperméthylation de l'ADN des reins a été observée sur deux générations de mâles nés de femelles exposées durant la gestation (alors que les profils de méthylation des reins des femelles n'étaient quant à eux pas modifiés). Une analyse multiomique réalisée à partir de l'ensemble des résultats d'analyses métabolomiques et transcriptomiques, met en évidence de nouvelles voies moléculaires associées aux effets de l'uranium. Ces analyses multiéchelles pourraient être utiles et pertinentes pour décrypter les mécanismes d'action des expositions chroniques à faibles doses d'uranium. Ces études mettent aussi en évidence l'importance du sexe dans l'estimation des sensibilités individuelles aux faibles doses, et attirent l'attention sur la nécessité de prendre en compte cette composante génétique en matière d'évaluation des risques.

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Low dose of uranium induces multigenerational epigenetic effects in rat kidney

Cited by 8 publications

References 45 publications

Use of omics analysis for low-dose radiotoxicology and health risk assessment: the case of uranium

Use of omics analysis for low-dose radiotoxicology and health risk assessment: the case of uranium

Multigenerational Exposure to Uranium Changes Sperm Metabolome in Rats

From metabolome to epigenome: example of multiscale analysis for studying the effects of low-dose uranium exposure

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