title: A mixture of the novel brominated flame retardants TBPH and TBB affects fecundity and transcript profiles of the HPGL-axis in Japanese medaka.
abstract: The novel brominated flame retardants (NBFRs), bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) and 2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) are components of the flame retardant mixture Firemaster 550 and both TBPH and TBB have recently been listed as high production volume chemicals by the US EPA. These NBFRs have been detected in several environmental matrices but very little is known about their toxic effects or potencies. Results of in vitro assays demonstrated potentials of these NBFRs to modulate endocrine function through interactions with estrogen (ER) and androgen receptors (AR) and via alterations to synthesis of 17-β-estradiol (E2) and testosterone (T), but in vivo effects of these chemicals on organisms are not known. Therefore a 21-day short term fish fecundity assay with Japanese medaka (Oryzias latipes) was conducted to investigate if these NBFRs affect endocrine function in vivo. Medaka were fed a diet containing either 1422 TBPH:1474 TBB or 138:144 μg/g food, wet weight (w/w). Cumulative production of eggs was used as a measure of fecundity and abundances of transcripts of 34 genes along the hypothalamus-pituitary-gonadal-liver (HPGL) axis were quantified to determine mechanisms of observed effects. Cumulative fecundity was impaired by 32% in medaka exposed to the greatest dose of the mixture of TBPH/TBB. A pattern of global down-regulation of gene transcription at all levels of the HPGL axis was observed, but effects were sex-specific. In female medaka the abundance of transcripts of ERβ was lesser in livers, while abundances of transcripts of VTG II and CHG H were greater. In male medaka, abundances of transcripts of ERα, ERβ, and ARα were lesser in gonads and abundances of transcripts of ERβ and ARα were lesser in brain. Abundances of transcripts of genes encoding proteins for synthesis of cholesterol (HMGR), transport of cholesterol (HDLR), and sex hormone steroidogenesis (CYP 17 and 3β-HSD) were significantly lesser in male medaka, which might have implications for concentrations of sex hormones. The results of this study demonstrate that exposure to components of the flame retardant mixture Firemaster(®) 550 has the potential to impair the reproductive axis of fishes.
authors.affiliation: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, Canada S7N 5B3. Electronic address: dms519@mail.usask.ca.
authors.forename: David M V
authors.initials: DM
authors.lastname: Saunders
authors.affiliation: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, Canada S7N 5B3.
authors.forename: Michelle
authors.initials: M
authors.lastname: Podaima
authors.affiliation: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, Canada S7N 5B3.
authors.forename: Garry
authors.initials: G
authors.lastname: Codling
authors.affiliation: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, Canada S7N 5B3; Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK, Canada S7N 5B3; Zoology Department, Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA; Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region; School of Biological Sciences, University of Hong Kong, Hong Kong Special Administrative Region; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK, Canada S7N 5B3.
authors.forename: Steve
authors.initials: S
authors.lastname: Wiseman
mesh_terms: D000818:Animals; D004703:Endocrine System / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005411:Flame Retardants / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006066:Gonads / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009990:Oryzias / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010902:Pituitary Gland / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D005411:Flame Retardants; D014874:Water Pollutants, Chemical
keywords: Endocrine disruption; Firemaster(®) 550; Novel brominated flame retardants; Reproduction