title: Epigenetic, histopathological and transcriptomic effects following exposure to depleted uranium in adult zebrafish and their progeny.
abstract: This study investigated the effects of adult zebrafish exposure to a nominal concentration of 20μgL-1of 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.
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115, France. Electronic address: kewin.gombeau@gmail.com.
authors.forename: Kewin
authors.initials: K
authors.lastname: Gombeau
authors.affiliation: Université de Bordeaux, CNRS, UMR 5805, EPOC, 33400 Talence, France. Electronic address: jean-paul.bourdineaud@u-bordeaux.fr.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bourdineaud
authors.affiliation: Univ. Grenoble Alpes, INAC-SyMMES, 38000 Grenoble, France; CEA, INAC-SCIB Laboratoire des Lésions des Acides Nucléiques, 38000 Grenoble, France. Electronic address: jean-luc.ravanat@cea.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115, France. Electronic address: olivier.armant@irsn.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Armant
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115, France. Electronic address: virginie.camilleri@irsn.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Camilleri
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115, France. Electronic address: isabelle.cavalie@irsn.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cavalie
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115, France. Electronic address: magali.floriani@irsn.fr.
authors.forename: Magali
authors.initials: M
authors.lastname: Floriani
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-ENV/SERIS/LECO, Cadarache, Saint-Paul-lez-Durance 13115, France. Electronic address: christelle.adam-guillermin@irsn.fr.
authors.forename: Christelle
authors.initials: C
authors.lastname: Adam-Guillermin
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005123:Eye / Q000187:drug effects; D005260:Female; D007814:Larva; D018482:Muscle, Skeletal / Q000187:drug effects*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*; D014501:Uranium / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014875:Water Pollutants, Radioactive / Q000633:toxicity; D015027:Zebrafish / Q000502:physiology*
chemical_list: D014874:Water Pollutants, Chemical; D014875:Water Pollutants, Radioactive; D014501:Uranium
keywords: DNA methylation; Depleted uraniums; Offspring; RNA sequencing; Zebrafish