G Elmhiri1, C Gloaguen1, S Grison1, D Kereselidze1, C Elie1, K Tack1, M Benderitter2, P Lestaevel1, A Legendre1, M Souidi3. 1. Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontenay-aux Roses, France; Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM, Fontenay-aux Roses, France. 2. Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM, SRBE, Fontenay-aux Roses, France; Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM, Fontenay-aux Roses, France. 3. Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM, SRBE, LRTOX, Fontenay-aux Roses, France; Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM, Fontenay-aux Roses, France. Electronic address: maamar.souidi@irsn.fr.
Abstract
INTRODUCTION: An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of chronic exposure to low doses of a radionuclide such as uranium remains unknown. Recently, a paradigm shift in the perception of risk of radiotoxicology has emerged through investigating the possibility of transmission of biological effects over generations, in particular by epigenetic pathways. These processes are known for their crucial roles associated with the development of several diseases. OBJECTIVE: The current work investigates the epigenetic effect of chronic exposure to low doses of uranium and its inheritance across generations. Materials and Methods To test this proposition, a rodent multigenerational model, males and females, were exposed to a non-toxic concentration of uranium (40mgL-1 drinking water) for nine months. The uranium effects on were evaluated over three generations (F0, F1 and F2) by analysing the DNA methylation profile and DNMT genes expression in ovaries and testes tissues. RESULTS: Here we report a significant hypermethylation of testes DNA (p <0.005) whereas ovaries showed hypomethylated DNA (p <0.005). Interestingly, this DNA methylation profile was significantly maintained across generations F0, F1 and F2. Furthermore, qPCR results of both tissues imply a significant change in the expression of DNA methyltransferase genes (DNMT 1 and DNMT3a/b) as well. CONCLUSION: Altogether, our work demonstrates for the first time a sex-dependance and inheritance of epigenetic marks, DNA methylation, as a biological response to the exposure to low doses of uranium. However, it is not clear which type of reproductive cell type is more responsive in this context.
INTRODUCTION: An increased health problem in industrialised countries is the contemporary concern of public and scientific community as well. This has been attributed in part to accumulated environmental pollutants especially radioactive substances and the use of nuclear power plants worldwide. However, the outcome of chronic exposure to low doses of a radionuclide such as uranium remains unknown. Recently, a paradigm shift in the perception of risk of radiotoxicology has emerged through investigating the possibility of transmission of biological effects over generations, in particular by epigenetic pathways. These processes are known for their crucial roles associated with the development of several diseases. OBJECTIVE: The current work investigates the epigenetic effect of chronic exposure to low doses of uranium and its inheritance across generations. Materials and Methods To test this proposition, a rodent multigenerational model, males and females, were exposed to a non-toxic concentration of uranium (40mgL-1 drinking water) for nine months. The uranium effects on were evaluated over three generations (F0, F1 and F2) by analysing the DNA methylation profile and DNMT genes expression in ovaries and testes tissues. RESULTS: Here we report a significant hypermethylation of testes DNA (p <0.005) whereas ovaries showed hypomethylated DNA (p <0.005). Interestingly, this DNA methylation profile was significantly maintained across generations F0, F1 and F2. Furthermore, qPCR results of both tissues imply a significant change in the expression of DNA methyltransferase genes (DNMT 1 and DNMT3a/b) as well. CONCLUSION: Altogether, our work demonstrates for the first time a sex-dependance and inheritance of epigenetic marks, DNA methylation, as a biological response to the exposure to low doses of uranium. However, it is not clear which type of reproductive cell type is more responsive in this context.
Authors: Nicole Redvers; Ann Marie Chischilly; Donald Warne; Manuel Pino; Amber Lyon-Colbert Journal: Environ Health Perspect Date: 2021-03-26 Impact factor: 9.031