Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-ENV/SRTE/LECO, Cadarache, Saint-Paul-lez-Durance, 13115, France.
Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SDOS/LMDN, Cadarache, Saint-Paul-lez-Durance, 13115, France.
Sci Rep. 2019 Dec 27;9(1):20241. doi: 10.1038/s41598-019-56590-w.
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.
切尔诺贝利和福岛第一核电站（NPP）灾难后，环境受到污染，导致大量人类和野生动物暴露于放射性物质中。然而，这些吸收放射性剂量所导致的亚致死后果仍研究不足，其长期的生物学影响也知之甚少。我们通过以 0.5 mGy/h、5 mGy/h 和 50 mGy/h 的剂量率暴露于放射性中，从受精开始直至受精后 120 小时（hpf），评估了慢性暴露于电离辐射（IR）对胚胎发育的生物学影响，从而涵盖了 6 mGy/h 定义的低剂量率领域。慢性暴露于 IR 会改变光暗运动测试中的幼虫行为，并在低至 0.5 mGy/h 的剂量率下影响心脏活动。转录组、蛋白质组和调控基因启动子转录因子结合位点的多组学分析表明，IR 慢性暴露后会导致神经发生、肌肉发育和视黄酸（RA）信号转导受到干扰。全胚胎 RNA 原位杂交证实，暴露胚胎的中枢神经系统中 her4.4 转录因子和发育中肌肉中的 myogenin 表达受损。在器官水平上，通过透射电子显微镜（TEM）评估肌肉组织学表明，在 5 mGy/h 和 50 mGy/h 时，暴露幼虫的肌纤维受到破坏，神经肌肉接头发生改变。这些多层次数据的整合表明，慢性暴露于低剂量率的 IR 会对神经元和肌肉祖细胞产生影响，从而导致 120 hpf 时自由游动幼虫的运动缺陷。对这些影响的机制理解使我们能够提出一个模型，即慢性暴露于 IR 会通过 RA 信号转导的失调对神经发生和肌肉发育产生多效性影响。
