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A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish.

ABSTRACT: Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120?hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to IR. Whole-mount RNA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of IR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.

SUBMITTER: Murat El Houdigui S

PROVIDER: S-EPMC6934629 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish.

Murat El Houdigui Sophia S Adam-Guillermin Christelle C Loro Giovanna G Arcanjo Caroline C Frelon Sandrine S Floriani Magali M Dubourg Nicolas N Baudelet Emilie E Audebert Stéphane S Camoin Luc L Armant Olivier O

Scientific reports 20191227 1

Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from ...[more]

PMID: 31882844

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Project description:The effects of ionising radiation (IR) on plants are important for environmental protection but also in agriculture, horticulture, space science, and plant stress biology. Much current understanding of the effects of IR on plants derives from acute high-dose studies but exposure to IR in the environment frequently occurs at chronic low dose rates. Chronic low dose-rate studies have primarily been field based and examined genetic or cytogenetic endpoints. Here we report research that investigated developmental, morphological and physiological effects of IR on Arabidopsis thaliana grown over 7 generations and exposed for five generations to chronic low doses of either 137Cs (at a dose rate of c. 40 ?Gy/h from ?/? emissions) or 10 ?M CdCl2. In some generations there were significant differences between treatments in the timing of key developmental phases and in leaf area or symmetry but there were, on the basis of the chosen endpoints, no long-term effects of the different treatments. Occasional measurements also detected no effects on root growth, seed germination rates or redox poise but in the generation in which it was measured exposure to IR did decrease DNA-methylation significantly. The results are consistent with the suggestion that chronic exposure to c. 40 ?Gy/h can have some effects on some traits but that this does not affect function across multiple generations at the population level. This is explained by the redundancy and/or degeneracy between biological levels of organization in plants that produces a relatively loose association between genotype and phenotype. The importance of this explanation to understanding plant responses to stressors such as IR is discussed. We suggest that the data reported here provide increased confidence in the Derived Consideration Reference Levels (DCRLs) recommended by the International Commission for Radiological Protection (ICRP) by providing data from controlled conditions and helping to contextualize effects reported from field studies. The differing sensitivity of plants to IR is not well understood and further investigation of it would likely improve the use of DCRLs for radiological protection.

Project description:BackgroundFew studies have investigated the toxicity and genotoxicity of extremely low frequency magnetic fields (ELF-MF) during prenatal and neonatal development. These phases of life are characterized by cell proliferation and differentiation, which might make them sensitive to environmental stressors. Although in vitro evidences suggest that ELF-MF may modify the effects of ionizing radiation, no research has been conducted so far in vivo on the genotoxic effects of ELF-MF combined with X-rays.Aim and methodsAim of this study was to investigate in somatic and germ cells the effects of chronic ELF-MF exposure from mid gestation until weaning, and any possible modulation produced by ELF-MF exposure on ionizing radiation-induced damage. Mice were exposed to 50 Hz, 65 μT magnetic field, 24 hours/day, for a total of 30 days, starting from 12 days post-conception. Another group was irradiated with 1 Gy X-rays immediately before ELF-MF exposure, other groups were only X-irradiated or sham-exposed. Micronucleus test on blood erythrocytes was performed at multiple times from 1 to 140 days after birth. Additionally, 42 days after birth, genotoxic and cytotoxic effects on male germ cells were assessed by comet assay and flow cytometric analysis.ResultsELF-MF exposure had no teratogenic effect and did not affect survival, growth and development. The micronucleus test indicated that ELF-MF induced a slight genotoxic damage only after the maximum exposure time and that this effect faded away in the months following the end of exposure. ELF-MF had no effects on ionizing radiation (IR)-induced genotoxicity in erythrocytes. Differently, ELF-MF appeared to modulate the response of male germ cells to X-rays with an impact on proliferation/differentiation processes. These results point to the importance of tissue specificity and development on the impact of ELF-MF on the early stages of life and indicate the need of further research on the molecular mechanisms underlying ELF-MF biological effects.

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A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish.

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A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish.

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