title: Developmental toxicity, EROD, and CYP1A mRNA expression in zebrafish embryos exposed to dioxin-like PCB126.
abstract: Dioxin-like PCB126 is a persistent organic pollutant that causes a range of syndromes including developmental toxicity. Dioxins have a high affinity for aryl hydrocarbon receptor (AhR) and induce cytochrome P4501A (CYP1A). However, the role of CYP1A activity in developmental toxicity is less clear. To better understand dioxin induced developmental toxicity, we exposed zebrafish (Danio rerio) embryos to PCB126 at concentrations of 0, 16, 32, 64, and 128 μg L(-1) from 3-h post-fertilization (hpf) to 168 hpf. The embryonic survival rate decreased at 144 and 168 hpf. The fry at 96 hpf displayed gross developmental malformations, including pericardial and yolk sac edema, spinal curvature, abnormal lower jaw growth, and non-inflated swim bladder. The pericardial and yolk sac edema rate significantly increased and the heart rate declined from 96 hpf compared with the controls. PCB126 did not alter the hatching rate. To elucidate the mechanism of PCB126-induced developmental toxicity, we conducted ethoxyresorufin-O-deethylase (EROD) in vivo assay to determine CYP1A enzyme activity, and real-time PCR to study the induction of CYP1A mRNA gene expression in embryo/larval zebrafish at 24, 72, 96, and 132 hpf. In vivo EROD activity was induced by PCB126 at 16 μg L(-1) concentration as early as 72 hpf but significant increases were observed only in zebrafish exposed to 64 and 128 μg L(-1) doses (p < 0.005) at 72, 96, and 132 hpf. Induction of CYP1A mRNA expression was significantly upregulated in zebrafish exposed to 32 and 64 μg L(-1) at 24, 72, 96, and 132 hpf. Overall, the severe pericardial and yolk sac edema and reduced heart rate suggest that heart defects are a sensitive endpoint, and the general trend of dose-dependent increase in EROD activity and induction of CYP1A mRNA gene expression provide evidence that the developmental toxicity of PCB126 to zebrafish embryos is mediated by activation of AhR.
authors.affiliation: Department of Veterinary Medicine, Agricultural College, Guangdong Ocean University, Zhanjiang, 524088, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Food Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, 524088, China.
authors.forename: Fang-Hong
authors.initials: FH
authors.lastname: Nie
authors.affiliation: Department of Veterinary Medicine, Agricultural College, Guangdong Ocean University, Zhanjiang, 524088, China.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Veterinary Medicine, Agricultural College, Guangdong Ocean University, Zhanjiang, 524088, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Veterinary Medicine, Agricultural College, Guangdong Ocean University, Zhanjiang, 524088, China.
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Ju
authors.affiliation: Department of Veterinary Medicine, Agricultural College, Guangdong Ocean University, Zhanjiang, 524088, China.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Wine, Food and Molecular Biosciences, Faculty of Agriculture and Life Sciences, Lincoln University, Lincoln, 7647, New Zealand.
authors.forename: Ravi
authors.initials: R
authors.lastname: Gooneratne
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian; D004785:Environmental Pollutants / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D007814:Larva; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D013723:Teratogens / Q000633:toxicity*; D015017:Yolk Sac / Q000187:drug effects
chemical_list: D004785:Environmental Pollutants; D012333:RNA, Messenger; D013723:Teratogens; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl
keywords: CYP1A; EROD; PCB126; developmental toxicity; zebrafish embryo