title: Transcriptional regulation in liver and testis associated with developmental and reproductive effects in male zebrafish exposed to natural mixtures of persistent organic pollutants (POP).
abstract: Persistent organic pollutants (POP) occur as mixtures in nature and it is difficult to predict the toxicity of such mixtures based on knowledge about toxicity and mechanisms of action for single compounds. The present knowledge on the combined toxic effects and modes of actions of exposure to mixtures is limited. Thus, the scientifically based hazard and risk assessment of POP requires analytical and toxicological data from studies with environmental mixtures of POP. The application of genome wide transcription profiling in toxicology, in combination with classical endpoints, will improve the current understanding of the mechanisms of toxic processes. Furthermore, gene expression data may be useful in establishing new hypothesis and discovering new biomarkers for known toxicity as well as not yet recognized toxicity endpoints. In the present study, developmental and reproductive effects of lifelong exposure to environmental relevant concentrations of two natural mixtures of POP were investigated using classical and molecular methods in a controlled zebrafish model. The mixtures used were extracted from burbot (Lota lota) liver originating from freshwater systems in Norway: one mixture with high levels and one mixture with background levels of polybrominated diphenyl ethers (PBD), polychlorinated biphenyls (PCB), and DDT. The concentration of POP in the zebrafish ranged from levels detected in wild fish from Lake Mjøsa, to concentrations reported in human and wildlife populations. Phenotypic effects observed in both exposure groups included (1) reduced survival, (2) earlier onset of puberty, (3) increased male/female sex ratio, and (4) differences in body weight at 5 mo of age. Interestingly, genome-wide transcription profiling showed changes in regulation of genes involved in endocrine signaling and growth. The transcriptomics changes included (1) key regulator genes for steroid and thyroid hormone functions (cga, ncoa3), (2) insulin signaling and metabolic homeostasis (pik3r1, pfkfb3, ptb1), and (3) p53 activation (mdm4). The effects observed in the experimental zebrafish model raise the question of whether chemical pollution represents a risk to the reproductive health of wild fish inhabiting the freshwater system.
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway. rasoul.nouri@veths.no
authors.forename: Rasoul
authors.initials: R
authors.lastname: Nourizadeh-Lillabadi
authors.forename: Jan L
authors.initials: JL
authors.lastname: Lyche
authors.forename: Camilla
authors.initials: C
authors.lastname: Almaas
authors.forename: Benedicte
authors.initials: B
authors.lastname: Stavik
authors.forename: S Jannicke
authors.initials: SJ
authors.lastname: Moe
authors.forename: Mona
authors.initials: M
authors.lastname: Aleksandersen
authors.forename: Vidar
authors.initials: V
authors.lastname: Berg
authors.forename: Kjetill S
authors.initials: KS
authors.lastname: Jakobsen
authors.forename: Nils Chr
authors.initials: NC
authors.lastname: Stenseth
authors.forename: Janneche Utne
authors.initials: JU
authors.lastname: Skåre
authors.forename: Peter
authors.initials: P
authors.lastname: Alestrøm
authors.forename: Erik
authors.initials: E
authors.lastname: Ropstad
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005618:Fresh Water; D048388:Gadiformes / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008136:Longevity / Q000187:drug effects; D008297:Male; D009930:Organic Chemicals / Q000633:toxicity; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics; D012744:Sex Ratio; D012741:Sexual Maturation / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D009930:Organic Chemicals; D014874:Water Pollutants, Chemical