Liu Yiran, Wu Ding, Xu Qinglong, Yu Liqin, Liu Chunsheng, Wang Jianghua
College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China.
Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
Aquat Toxicol. 2017 Oct;191:17-24. doi: 10.1016/j.aquatox.2017.07.015. Epub 2017 Jul 27.
Tris (2-butoxyethyl) phosphate (TBOEP), is used as a flame retardant worldwide. It is an additive in materials and can be easily discharged into the surrounding environment. There is evidence linking TBOEP exposure to abnormal development and growth in zebrafish embryos/larvae. Here, using zebrafish embryo as a model, we investigated toxicological effects on developing zebrafish (Danio rerio) caused by TBOEP at concentrations of 0, 20, 200, 1000, 2000μg/L starting from 2h post-fertilization (hpf). Our findings revealed that TBOEP exposure caused developmental toxicity, such as malformation, growth delay and decreased heart rate in zebrafish larvae. Correlation analysis indicated that inhibition of growth was possibly due to down-regulation of expression of genes related to the growth hormone/insulin-like growth factor (GH/IGF) axis. Furthermore, exposure to TBOEP significantly increased thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in whole larvae. In addition, changed expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis was observed, indicating that perturbation of HPT axis might be responsible for the developmental damage and growth delay induced by TBOEP. The present study provides a new set of evidence that exposure of embryo-larval zebrafish to TBOEP can cause perturbation of GH/IGF axis and HPT axis, which could result in developmental impairment and growth inhibition.
磷酸三（2-丁氧基乙基）酯（TBOEP）在全球范围内用作阻燃剂。它是材料中的一种添加剂，很容易排放到周围环境中。有证据表明，接触TBOEP与斑马鱼胚胎/幼体的异常发育和生长有关。在此，我们以斑马鱼胚胎为模型，研究了从受精后2小时（hpf）开始，浓度为0、20、200、1000、2000μg/L的TBOEP对发育中的斑马鱼（Danio rerio）的毒理学影响。我们的研究结果显示，接触TBOEP会导致斑马鱼幼体出现发育毒性，如畸形、生长延迟和心率降低。相关性分析表明，生长受到抑制可能是由于生长激素/胰岛素样生长因子（GH/IGF）轴相关基因的表达下调。此外，接触TBOEP会使整个幼体中的甲状腺素（T4）和3,5,3'-三碘甲状腺原氨酸（T3）显著增加。此外，还观察到下丘脑-垂体-甲状腺（HPT）轴相关基因的表达发生了变化，这表明HPT轴的紊乱可能是TBOEP诱导发育损伤和生长延迟的原因。本研究提供了一组新的证据，即斑马鱼胚胎幼体接触TBOEP会导致GH/IGF轴和HPT轴紊乱，进而导致发育障碍和生长抑制。
