In utero exposure to ionizing radiation and metabolic regulation: perspectives for future multi- and trans-generation effects studies

Abstract

Purpose

The radiation protection community has been particularly attentive to the risks of delayed effects on offspring from low dose or low dose-rate exposures to ionizing radiation. Despite this, the current epidemiologic studies and scientific data are still insufficient to provide the necessary evidence for improving risk assessment guidelines. This literature review aims to inform future studies on multigenerational and transgenerational effects. It primarily focuses on animal studies involving in utero exposure and discusses crucial elements for interpreting the results. These elements include in utero exposure scenarios relative to the developmental stages of the embryo/fetus, and the primary biological mechanisms responsible for transmitting heritable or hereditary effects to future generations. The review addresses several issues within the contexts of both multigenerational and transgenerational effects, with a focus on hereditary perspectives.

Conclusions

Knowledge consolidation in the field of Developmental Origins of Health and Disease (DOHaD) has led us to propose a new study strategy. This strategy aims to address the transgenerational effects of in utero exposure to low dose and low dose-rate radiation. Within this concept, there is a possibility that disruption of epigenetic programming in embryonic and fetal cells may occur. This disruption could lead to metabolic dysfunction, which in turn may cause abnormal responses to future environmental challenges, consequently increasing disease risk. Lastly, we discuss methodological limitations in our studies. These limitations are related to cohort size, follow-up time, model radiosensitivity, and analytical techniques. We propose scientific and analytical strategies for future research in this field.

Keywords:

• Low dose
• ionizing radiation
• in utero
• multigenerational
• co-exposure
• multifactorial disease
• oxidative stress

Acknowledgments

The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

Stéphane Grison

Stéphane Grison, PhD, is a researcher in radiobiology/radiotoxicology at the Institût de Radioprotection et de Sûreté Nucléaire (France). His research focuses on the effects of low doses of ionizing radiation, with the main aim of understanding the mechanisms of early molecular responses and how they may contribute to long-term effects on offspring and subsequent generations.

Ignacia III Braga-Tanaka

Ignacia III Braga-Tanaka, DVM, PhD is a veterinary pathologist and is a senior researcher in the Department of Radiobiology at the Institute for Environmental Sciences. She investigates the late effects (neoplastic and non-neoplastic disease) of chronic low dose-rate radiation exposure on mice.

Sarah Baatout

Sarah Baatout is head of the Radiobiology Unit at the Belgian Nuclear Research Center, guest professor at Gent University and maître de conférence at University of Namur.

Dmitry Klokov

Dmitry Klokov, Ph.D., is a head of the Laboratory of Experimental Radiotoxicology and Radiobiology (LRTOX), Institute of Radioprotection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France. He also holds an Adjunct Professor position at the Department of Biochemistry, Microbiology and Immunology of University of Ottawa. Previously, Dmitry Klokov has led a low dose radiobiology program at the Canadian Nuclear Laboratories. His research interests include various domains within the field of low dose radiation effects, with an overarching goal to understand mechanisms of early genotoxic and molecular responses and how they may contribute to long-term health outcomes, such as cancer, cardiovascular and neurological pathologies, and transgenerational effects. Dmitry Klokov has also been involved in various international initiatives in low dose radiobiological research and cooperation, including those coordinated by UNSCEAR, NEA, MELODI, DOE and others.