title: Effects of tris (2-butoxyethyl) phosphate (TBOEP) on endocrine axes during development of early life stages of zebrafish (Danio rerio).
abstract: Due to phasing out of additive flame retardants such as polybrominated diphenyl ethers (PBDEs), Tris (2-butoxyethyl) phosphate (TBOEP) is widely used as a substitute. TBOEP is ubiquitous in the environment and has been measured at concentrations of micrograms per liter (μg L(-1)) in surface waters and wastewater. Information on potential adverse effects on development of aquatic organisms caused by exposure to environmentally relevant concentrations of TBOEP is limited, especially for effects that may be caused through impairment of endocrine-modulated homeostasis. Therefore, this study was conducted to determine effects of TBOEP on ontogeny and transcription profiles of genes along the hypothalamus-pituitary-thyroidal (HPT), hypothalamus-pituitary-adrenal (HPA), and hypothalamus-pituitary-gonadal (HPG) axes in embryos/larvae of zebrafish (Danio rerio). Exposure to TBOEP (2-5,000 μg L(-1)) from 3 h post-fertilization (hpf) to 120 hpf induced developmental malformations in zebrafish with a LC50 of 288.54 μg L(-1) at both 96 hpf and 120 hpf. The predicted no observed effect concentration (PNOEC) was 2.40 μg L(-1). Exposure to 2, 20, or 200 μg TBOEP L(-1) altered expression of genes involved in three major molecular pathways in a concentration-dependent manner after 120 hpf. TBOEP caused lesser expression of some genes involved in synthesis of hormones, such as (pomc and fshβ) as well as upregulating expression of some genes coding for receptors (thr, tshr, gr, mr, er and ar) in zebrafish larvae. These changes at the molecular level could result in alterations of endocrine function, which could result in edema or deformity and ultimately death.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Ma
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, 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, 210023, China.
authors.forename: Yueqiu
authors.initials: Y
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 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, 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, 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; School of Biological Sciences, University of Hong Kong, Hong Kong, China.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: Toxicology Centre, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada.
authors.forename: David M V
authors.initials: DM
authors.lastname: Saunders
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, 210023, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D004703:Endocrine System / Q000187:drug effects* / Q000502:physiology; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D007928:Lethal Dose 50; D008018:Life Cycle Stages / Q000187:drug effects*; D009024:Morphogenesis / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity*; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000254:growth & development* / Q000378:metabolism
chemical_list: D009943:Organophosphorus Compounds; D014874:Water Pollutants, Chemical; C013320:tris(2-butoxyethyl) phosphate
keywords: Endocrine axes; Endocrine disruptor; Environmentally relevant; Organophosphate flame retardant; qRT-PCR