title: Aryl hydrocarbon receptor 2 mediates the toxicity of Paclobutrazol on the digestive system of zebrafish embryos.
abstract: Paclobutrazol (PBZ), a trazole-containing fungicide and plant growth retardant, has been widely used for over 30 years to regulate plant growth and promote early fruit setting. Long-term usage of PBZ in agriculture and natural environments has resulted in residual PBZ in the soil and water. Chronic exposure to waterborne PBZ can cause various physiological effects in fish, including hepatic steatosis, antioxidant activity, and disruption of spermatogenesis. We have previously shown that PBZ also affects the rates of zebrafish embryonic survival and hatching, and causes developmental failure of the head skeleton and eyes; here, we further show that PBZ has embryonic toxic effects on digestive organs of zebrafish, and describe the underlying mechanisms. PBZ treatment of embryos resulted in dose-dependent morphological and functional abnormalities of the digestive organs. Real-time RT-PCR and in situ hybridization were used to show that PBZ strongly induces cyp1a1 expression in the digestive system, and slightly induces ahr2 expression in zebrafish embryos. Knockdown of ahr2 with morpholino oligonucleotides prevents PBZ toxicity. Thus, the toxic effect of PBZ on digestive organs is mediated by AhR2, as was previously reported for retene and TCDD. These findings have implications for understanding the potential toxicity of PBZ during embryogenesis, and thus the potential impact of fungicides on public health and the environment.
authors.affiliation: Department of Bio-Agricultural Sciences, National Chiayi University, Chiayi City, Taiwan. Electronic address: wangw4@mail.ncyu.edu.tw.
authors.forename: Wen-Der
authors.initials: WD
authors.lastname: Wang
authors.affiliation: Department of Bio-Agricultural Sciences, National Chiayi University, Chiayi City, Taiwan.
authors.forename: Guan-Ting
authors.initials: GT
authors.lastname: Chen
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei City, Taiwan.
authors.forename: Hwei-Jan
authors.initials: HJ
authors.lastname: Hsu
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung City, Taiwan.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wu
mesh_terms: D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004064:Digestive System / Q000187:drug effects* / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005659:Fungicides, Industrial / Q000633:toxicity; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D014230:Triazoles / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C474372:AHR2 protein, zebrafish; D005659:Fungicides, Industrial; D018336:Receptors, Aryl Hydrocarbon; D014230:Triazoles; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C053370:paclobutrazol; D019363:Cytochrome P-450 CYP1A1
keywords: Aryl hydrocarbon receptor; Cyp1a1; Digestive organs; Paclobutrazol; Zebrafish