Epigenetic, histopathological and transcriptomic effects following exposure to depleted uranium in adult zebrafish...

This study investigated the effects of adult zebrafish exposure to a nominal concentration of 20μgL^-1 of depleted uranium (DU) for six days upon DNA methylation, gene expression and the appearance of histopathological damage in their progeny. In the embryos at the 2-8 cell stage, the parental exposure induced significant DU accumulation, with levels seven times higher than those measured in the control embryos, but in larvae 96h post-fertilisation (hpf), uranium concentration had already returned to a level identical to that of the control larvae. A significant two-fold increase in the global level of DNA methylation was observed in embryos as early as the prim5 (24 hpf) stage and was still maintained at the 96 hpf stage despite the fact that DU had already been depurated at the later stage. RNA sequencing analysis indicated an impact of parental exposure upon the total RNAs transmitted from the mother to eggs, and the up-regulated genes were those associated with post-traductional protein modification and trafficking and cellular signalling pathways, whereas the down-regulated genes concerned the translational process, cell cycle regulation and several cell signalling pathways. Alterations of photoreceptor cells and the axon-axon junctions between photoreceptors were observed in the eyes of adult fish exposed for 10days to DU. Actin and myosin filament disorganisation was observed in the skeletal muscles of 96 hpf larvae, at a stage when the maternally transmitted DU had already been excreted. These data reveal the extreme sensitivity of zebrafish embryos to DU transmitted through the oocyte by exposed females.