Zhang Wanglong, Zong Yanjiao, Sun Ruize, Xue Zhenhong, Wan Wenhui, Ren Anran, Ma Yongchao, Tian Wenjing, Wang Renjun
College of Life Sciences, Qufu Normal University, Qufu, Shandong 273165, PR China.
College of Life Sciences, Qufu Normal University, Qufu, Shandong 273165, PR China.
Aquat Toxicol. 2025 May;282:107323. doi: 10.1016/j.aquatox.2025.107323. Epub 2025 Mar 9.
The global water pollution now calls for precise risk assessment of chemicals, e.g., dioxins and the dioxin-like compounds (DLCs). The freshwater and marine medaka have been widely implemented in the toxicity testing, and perhaps give mechanistic information for comparative biology. The question that 'will they report equal results due to their close phylogenetic relation' has been raised, therefore, we explored their physiological and molecular responses to dioxin. As the mediator of the dioxin toxicity, the aryl hydrocarbon receptor (AHR) of marine medaka (Oryzias melastigma) has not been functionally characterized and might be species-specific. In terms of sensitivity to dioxin-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the EC values of omeAHR1a (0.16±0.12 nM), omeAHR1b (2.96±2.96 nM), omeAHR2a (0.44±0.30 nM), and omeAHR2b (9.00±6.88 nM) exhibit marked variations. The omeAHR2a and omeAHR1a display heightened sensitivity compared to the freshwater Japanese medaka (Oryzias latipes) counterparts olaAHR2a and olaAHR1a, respectively. The results indicate the in vitro sensitivity of AHR among species can vary by one or two orders of magnitude. Further mechanistic investigations using additional ligands and computational modeling reveal that: 1) most of omeAHR2a, olaAHR2a, dreAHR2, and hsaAHR interact with ligands in the affinity order of TCDD > PCB126 > BNF > indole, mirroring their AHR transactivation potency, but the docking poses and dynamics can vary; 2) one AHR subform's high sensitivity to dioxin-TCDD may extend to DLCs but not to other types of ligands. Beyond the in vitro study, the preliminary in vivo LC data indicate that marine medaka (LC: 1.64 ng/L (95 % CI: 1.05-2.55 ng/L)) has similar sensitivity, and possibly slightly greater (not statistically determined yet), to TCDD in comparison with Japanese medaka (LC: 3.42 ng/L (95 % CI: 1.37-6.48 ng/L)).These insights underscore the difference of AHR biology among species even the close relative species, and point out the necessity for meticulous consideration when evaluating the toxicity of compounds and when extending predictive toxicity assessments to more species.
全球水污染问题现在需要对化学物质进行精确的风险评估，例如二噁英和二噁英类化合物（DLCs）。淡水和海水青鳉已广泛应用于毒性测试中，并且可能为比较生物学提供机制信息。因此，有人提出了“由于它们的系统发育关系密切，它们会报告相同的结果吗”这一问题，我们探索了它们对二噁英的生理和分子反应。作为二噁英毒性的介质，海水青鳉（Oryzias melastigma）的芳烃受体（AHR）尚未进行功能表征，可能具有物种特异性。就对二噁英-2,3,7,8-四氯二苯并对二噁英（TCDD）的敏感性而言，omeAHR1a（0.16±0.12 nM）、omeAHR1b（2.96±2.96 nM）、omeAHR2a（0.44±0.30 nM）和omeAHR2b（9.00±6.88 nM）的EC值表现出显著差异。omeAHR2a和omeAHR1a分别比淡水日本青鳉（Oryzias latipes）的对应物olaAHR2a和olaAHR1a表现出更高的敏感性。结果表明，物种间AHR的体外敏感性可能相差一到两个数量级。使用其他配体和计算模型进行的进一步机制研究表明：1）omeAHR2a、olaAHR2a、dreAHR2和hsaAHR中的大多数与配体的相互作用亲和力顺序为TCDD > PCB126 > BNF > 吲哚，反映了它们的AHR反式激活能力，但对接姿势和动力学可能不同；2）一种AHR亚型对二噁英-TCDD的高敏感性可能扩展到DLCs，但不适用于其他类型的配体。除了体外研究，初步的体内LC数据表明，与日本青鳉（LC：3.42 ng/L（95% CI：1.37 - 6.48 ng/L））相比，海水青鳉（LC：1.64 ng/L（95% CI：1.05 - 2.55 ng/L））对TCDD具有相似的敏感性，并且可能略高（尚未进行统计学测定）。这些见解强调了即使是亲缘关系密切的物种之间AHR生物学的差异，并指出在评估化合物毒性以及将预测毒性评估扩展到更多物种时进行细致考虑的必要性。
