Centre for Organismal Studies, Aquatic Ecology and Toxicology, University of Heidelberg, Im Neuenheimer Feld 504, 69120 Heidelberg, Germany.
Vetsuisse Faculty, Centre for Fish and Wildlife Health, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland.
Int J Mol Sci. 2019 Mar 27;20(7):1543. doi: 10.3390/ijms20071543.
The effects of thyroid hormone disrupting chemicals (THDCs) on eye development of zebrafish were investigated. We expected THDC exposure to cause transcriptional changes of vision-related genes, which find their phenotypic anchoring in eye malformations and dysfunction, as observed in our previous studies. Zebrafish were exposed from 0 to 5 days post fertilization (dpf) to either propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, or tetrabromobisphenol-A (TBBPA), which interacts with thyroid hormone receptors. Full genome microarray analyses of RNA isolated from eye tissue revealed that the number of affected transcripts was substantially higher in PTU- than in TBBPA-treated larvae. However, multiple components of phototransduction (e.g., phosphodiesterase, opsins) were responsive to both THDC exposures. Yet, the response pattern for the gene ontology (GO)-class "sensory perception" differed between treatments, with over 90% down-regulation in PTU-exposed fish, compared to over 80% up-regulation in TBBPA-exposed fish. Additionally, the reversibility of effects after recovery in clean water for three days was investigated. Transcriptional patterns in the eyes were still altered and partly overlapped between 5 and 8 dpf, showing that no full recovery occurred within the time period investigated. However, pathways involved in repair mechanisms were significantly upregulated, which indicates activation of regeneration processes.
研究了甲状腺激素干扰化学物质（THDC）对斑马鱼眼睛发育的影响。我们预计 THDC 暴露会导致与视觉相关基因的转录变化，这些基因的表型在眼睛畸形和功能障碍中得到了体现，正如我们之前的研究中观察到的那样。从受精后 0 到 5 天（dpf），将斑马鱼暴露于甲状腺激素合成抑制剂丙基硫氧嘧啶（PTU）或与甲状腺激素受体相互作用的四溴双酚 A（TBBPA）中。从眼部组织分离的 RNA 的全基因组微阵列分析表明，受影响的转录本数量在 PTU 处理的幼虫中明显高于 TBBPA 处理的幼虫。然而，光转导的多个组成部分（例如，磷酸二酯酶，视蛋白）对两种 THDC 暴露都有反应。然而，基因本体论（GO）类“感觉感知”的反应模式在处理之间存在差异，与 TBBPA 暴露的鱼类相比，PTU 暴露的鱼类中有超过 90％的下调，而 TBBPA 暴露的鱼类中有超过 80％的上调。此外，还研究了在清洁水中恢复三天后效应的可逆性。在 5 至 8 dpf 之间，眼睛中的转录模式仍然发生改变并且部分重叠，表明在研究的时间段内没有完全恢复。然而，参与修复机制的途径显著上调，这表明激活了再生过程。
