Biology, Örebro Life Science Center, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
Aquat Toxicol. 2013 Oct 15;142-143:63-72. doi: 10.1016/j.aquatox.2013.07.018. Epub 2013 Aug 6.
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.
四溴乙基环己烷（TBECH）是一种溴化阻燃剂，已被证明是人类雄激素受体（AR）的有效激动剂。然而，尽管它存在于环境中，但尚不清楚它是否与水生物种的 AR 相互作用。因此，本研究旨在利用斑马鱼作为模型生物，增进我们对 TBECH 如何影响水生动物的理解。计算机模拟表明，TBECH 对映异构体与斑马鱼雄激素受体（zAR）结合，体外和体内数据表明 TBECH 具有雄激素特性。研究了 TBECH 对胚胎和幼鱼的有害影响，并进行了体外和体内的 qRT-PCR 分析，以确定 TBECH 对基因调控的影响。结果发现，TBECH 在 1μM 和 10μM 剂量下延迟孵化，而在 10μM 时观察到形态异常和幼鱼死亡。qRT-PCR 分析显示，参与软骨发生（软骨发育）、代谢和应激反应的多个基因发生改变。因此，TBECH 诱导雄激素活性，并对斑马鱼的生理产生负面影响，因此应对其对环境的影响进行仔细监测。
