title: Differential modulation of expression of nuclear receptor mediated genes by tris(2-butoxyethyl) phosphate (TBOEP) on early life stages of zebrafish (Danio rerio).
abstract: As one substitute for phased-out brominated flame retardants (BFRs), tris(2-butoxyethyl) phosphate (TBOEP) is frequently detected in aquatic organisms. However, knowledge about endocrine disrupting mechanisms associated with nuclear receptors caused by TBOEP remained restricted to results from in vitro studies with mammalian cells. In the study, results of which are presented here, embryos/larvae of zebrafish (Danio rerio) were exposed to 0.02, 0.1 or 0.5μM TBOEP to investigate expression of genes under control of several nuclear hormone receptors (estrogen receptors (ERs), androgen receptor (AR), thyroid hormone receptor alpha (TRα), mineralocorticoid receptor (MR), glucocorticoid receptor (GR), aryl hydrocarbon (AhR), peroxisome proliferator-activated receptor alpha (PPARα), and pregnane×receptor (P×R)) pathways at 120hpf. Exposure to 0.5μM TBOEP significantly (p<0.05, one-way analysis of variance) up-regulated expression of estrogen receptors (ERs, er1, er2a, and er2b) genes and ER-associated genes (vtg4, vtg5, pgr, ncor, and ncoa3), indicating TBOEP modulates the ER pathway. In contrast, expression of most genes (mr, 11βhsd, ube2i,and adrb2b) associated with the mineralocorticoid receptor (MR) pathway were significantly down-regulated. Furthermore, in vitro mammalian cell-based (MDA-kb2 and H4IIE-luc) receptor transactivation assays, were also conducted to investigate possible agonistic or antagonistic effects on AR- and AhR-mediated pathways. In mammalian cells, none of these pathways were affected by TBOEP at the concentrations studied. Receptor-mediated responses (in vivo) and mammalian cell lines receptor binding assay (in vitro) combined with published information suggest that TBOEP can modulate receptor-mediated, endocrine process (in vivo/in vitro), particularly ER and MR.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: zhiyuan_nju@163.com.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: yjun.yu@gmail.com.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.
authors.forename: Song
authors.initials: S
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China. Electronic address: hlliu@nju.edu.cn.
authors.forename: Hongling
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China.
authors.forename: Guanyong
authors.initials: G
authors.lastname: Su
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China; Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: School of Environment and Sustainability, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, Jiangsu 210023, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009943:Organophosphorus Compounds / Q000633:toxicity*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000502:physiology*
chemical_list: D009943:Organophosphorus Compounds; D018160:Receptors, Cytoplasmic and Nuclear; D014874:Water Pollutants, Chemical; C013320:tris(2-butoxyethyl) phosphate
keywords: Endocrine disruption; Estrogen receptor; Flame retardant; Mineralocorticoid receptor; Nuclear receptor; Organophosphate; Receptor-mediated network; Toxicity