title: The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances.
abstract: Tetrabromoethylcyclohexane (TBECH) is a brominated flame retardant that has been shown to be a potent agonist to the human androgen receptor (AR). However, while it is present in the environment, it is not known if it interacts with AR from aquatic species. The present study was therefore aimed at improving our understanding of how TBECH affects aquatic animals using zebrafish as a model organism. In silico modeling demonstrated that TBECH diastereomers bind to the zebrafish androgen receptor (zAR) and in vitro and in vivo data showed that TBECH has androgenic properties. Deleterious effects of TBECH were studied on embryonic and juvenile zebrafish and qRT-PCR analysis in vitro and in vivo was performed to determine TBECH effects on gene regulation. TBECH was found to delay hatching at 1 μM and 10 μM doses while morphological abnormalities and juvenile mortality was observed at 10 μM. The qRT-PCR analysis showed alterations of multiple genes involved in chondrogenesis (cartilage development), metabolism and stress response. Thus, TBECH induces androgenic activity and has negative effects on zebrafish physiology and therefore its impact on the environment should be carefully monitored.
authors: Biology, Örebro Life Science Center, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
authors: Ajay
authors: A
authors: Pradhan
authors: Joubert Banjop
authors: JB
authors: Kharlyngdoh
authors: Solomon
authors: S
authors: Asnake
authors: Per-Erik
authors: PE
authors: Olsson
mesh_terms: D000818:Animals; D002460:Cell Line; D003510:Cyclohexanes / Q000633:toxicity*; D004625:Embryo, Nonmammalian; D005786:Gene Expression Regulation / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D011944:Receptors, Androgen / Q000235:genetics*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*
chemical_list: D003510:Cyclohexanes; D011944:Receptors, Androgen; D014874:Water Pollutants, Chemical; C517232:1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane
keywords: Androgens; Endocrine; Endocrine disruptor; Gene regulation