title: Effects of the brominated flame retardant TBCO on fecundity and profiles of transcripts of the HPGL-axis in Japanese medaka.
abstract: The novel brominated flame retardant, 1,2,5,6-tetrabromocyclooctane (TBCO) is an additive flame retardant which is marketed under the trade name Saytex BCL-48. TBCO has recently been investigated as a potential alternative to the major use brominated flame retardant, hexabromocyclododecane (HBCD), which could have major implications for significant increases in amounts of TBCO used. Yet there is a lack of information regarding potential toxicities of TBCO. Recently, results of in vitro experiments have demonstrated the potential of TBCO to modulate endocrine function through interaction with estrogen and androgen receptors and via alterations to the synthesis of 17-β-estradiol and testosterone. Further research is required to determine potential endocrine disrupting effects of TBCO in vivo. In this experiment a 21-day fecundity assay with Japanese medaka (Oryzias latipes) was conducted to examine endocrine disrupting effects of TBCO in vivo. Medaka were fed a diet containing either 607 or 58μg TBCO/g food, wet mass (wm). Fecundity, measured as cumulative deposition of eggs and fertilization of eggs, as well as abundances of transcripts of 34 genes along the hypothalamus-pituitary-gonadal-liver (HPGL) axis were measured as indicators of holistic endocrine disruption and to determine mechanisms of effects, respectively. Cumulative fecundity was 18% lesser by medaka exposed to 58μg TBCO/g, wm food. However, fecundity of medaka exposed to 607μg TBCO/g, wm food was not significantly different from that of controls. Organ-specific and dose-dependent alterations to abundances of transcripts were observed in male and female medaka. A pattern of down-regulation of expression of genes involved in steroidogenesis, metabolism of cholesterol, and regulatory feedback mechanisms was observed in gonads from male and female medaka which had been exposed to the greater concentration of TBCO. However, these effects on expression of genes were not manifested in effects on fertilization of eggs or fecundity. In livers from male and female medaka exposed to the lesser concentration of TBCO greater expression of genes that respond to exposure to estrogens, including vitellogenin II, choriogenin H, and ERα, were observed. The results reported here confirm the endocrine disrupting potential of TBCO and elucidate potential mechanisms of effects which include specific patterns of alterations to abundances of transcripts of genes in the gonad and liver of medaka.
authors: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada. Electronic address: dms519@mail.usask.ca.
authors: David M V
authors: DM
authors: Saunders
authors: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada.
authors: Michelle
authors: M
authors: Podaima
authors: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada.
authors: Steve
authors: S
authors: Wiseman
authors: Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada; Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B3, Canada; 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, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, People's Republic of China.
authors: John P
authors: JP
authors: Giesy
mesh_terms: D000818:Animals; D034242:Cyclooctanes / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D029941:Fish Proteins / Q000235:genetics; D005411:Flame Retardants / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006066:Gonads / Q000187:drug effects; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D009990:Oryzias / Q000502:physiology; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: C540596:1,2,5,6-tetrabromocyclooctane; D034242:Cyclooctanes; D052244:Endocrine Disruptors; D029941:Fish Proteins; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D014819:Vitellogenins; D014874:Water Pollutants, Chemical
keywords: Endocrine disruption; Fish; Novel brominated flame retardants; Reproduction