State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Aquat Toxicol. 2013 Jan 15;126:207-13. doi: 10.1016/j.aquatox.2012.11.009. Epub 2012 Nov 19.
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in the environment and in various biota, including fish, and has been implicated in disruption of the thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to different concentrations of TDCPP (10, 50, 100, 300 and 600 μg/L) from 2 h post-fertilization (hpf) to 144 hpf. Developmental endpoints, and whole-body concentrations of thyroid hormones and transcriptional profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were examined. Exposure to TDCPP caused a dose-dependent developmental toxicity, including decreased body weight, reduced hatching, survival and heartbeat rates, and increased malformation (spinal curvature). Treatment with the positive control chemical 3,3',5-triiodo-l-thyronine (T3) significantly decreased whole-body thyroxin (T4) concentrations, increased whole-body T3 concentrations, and upregulated mRNA expression involved in the HPT axis as a compensatory mechanism. These results suggested that the HPT axis in 144-hpf zebrafish larvae was responsive to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. TDCPP exposure significantly decreased whole-body T4 concentrations and increased whole-body T3 concentrations, indicating thyroid endocrine disruption. The upregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) might be responsible for decreased T4 concentrations. Treatment with TDCPP also significantly increased transcription of genes involved in thyroid hormone synthesis (tshβ, slc5a5 and tg) and thyroid development (hhex, nkx2.1 and pax8) as a compensatory mechanism for decreased T4 concentrations. Taken together, these results suggest that TDCPP alters the transcription of genes involved in the HPT axis and changes whole-body concentrations of thyroid hormones in zebrafish embryos/larvae, thus causing an endocrine disruption of the thyroid system.
三（1,3-二氯-2-丙基）磷酸酯（TDCPP）已在环境和各种生物群中频繁检出，包括鱼类，并被认为会破坏甲状腺内分泌系统。在本研究中，从受精后 2 小时（hpf）至 144 hpf，将斑马鱼（Danio rerio）胚胎暴露于不同浓度的 TDCPP（10、50、100、300 和 600μg/L）中。检查了发育终点、甲状腺激素的全身浓度以及参与下丘脑-垂体-甲状腺（HPT）轴的基因的转录谱。TDCPP 暴露引起了剂量依赖性的发育毒性，包括体重减轻、孵化、存活率和心跳率降低，以及畸形（脊柱弯曲）增加。用阳性对照化学物质 3,3',5-三碘甲状腺原氨酸（T3）处理，显著降低了全身甲状腺素（T4）浓度，增加了全身 T3 浓度，并上调了 HPT 轴相关基因的 mRNA 表达，作为一种代偿机制。这些结果表明，144 hpf 斑马鱼幼虫的 HPT 轴对化学物质暴露有反应，可以用于评估化学物质对甲状腺内分泌系统的影响。TDCPP 暴露显著降低了全身 T4 浓度并增加了全身 T3 浓度，表明甲状腺内分泌紊乱。与甲状腺激素代谢（dio1 和 ugt1ab）相关的基因上调可能是 T4 浓度降低的原因。TDCPP 处理还显著增加了甲状腺激素合成（tshβ、slc5a5 和 tg）和甲状腺发育（hhex、nkx2.1 和 pax8）相关基因的转录，作为降低 T4 浓度的代偿机制。综上所述，这些结果表明，TDCPP 改变了 HPT 轴中涉及的基因的转录，并改变了斑马鱼胚胎/幼虫全身甲状腺激素的浓度，从而导致甲状腺系统的内分泌紊乱。
