基于代谢组学技术分析磷酸三苯酯诱导斑马鱼胚胎发育毒性的分子机制
作者简介:
张杏丽(1987-),女,博士,研究方向为新型有机污染物的生态毒理与分子机制研究,E-mail:zhangxingli@htu.edu.cn
- 1. 河南师范大学环境学院, 黄淮水环境与污染防治教育部重点实验室, 河南省环境污染控制重点实验室, 新乡 453007;
- 2. 南开大学环境科学与工程学院, 环境污染过程与基准教育部重点实验室, 天津市城市生态环境修复与污染防治重点实验室, 天津 300071
摘要: 磷酸三苯酯(TPhP)是广泛存在于环境介质和生物体内的一种典型有机磷阻燃剂。为探求TPhP诱发水生动物发育毒性的分子机制，本研究以斑马鱼为模式动物，将发育至2.5 hpf (hours post fertilization)的斑马鱼胚胎暴露于0.0025、0.1、1、10、100和1 000 μg·L-1 TPhP溶液至7 dpf (days post fertilization)，考察斑马鱼胚胎生长发育指标和线粒体功能的变化，通过代谢组学分析揭示相关分子机制。结果表明，环境相关浓度(0.0025、0.1和1 μg·L-1)TPhP对斑马鱼胚胎发育无显著影响，但是轻微干扰了斑马鱼的代谢过程。100和1 000 μg·L-1 TPhP暴露引起斑马鱼心跳速率、孵化率和线粒体膜电位明显下调，畸形率分别增加6.8倍和12.5倍，死亡率分别增加7.2倍和16.5倍。代谢组学分析发现，10、100和1 000 μg·L-1 TPhP显著抑制斑马鱼氨基酸代谢，降低缬氨酸、亮氨酸和异亮氨酸水平，抑制氨酰-tRNA生物合成过程；同时引起葡萄糖糖酵解过程和三羧酸循环发生障碍。氨基酸和糖代谢异常可能是TPhP引起斑马鱼发育畸形的主要原因，线粒体功能紊乱可能是TPhP诱发三羧酸循环障碍的原因。上述研究结果为TPhP发育毒性机制分析提供了新思路。
Molecular Mechanisms of Developmental Toxicity of Triphenyl Phosphate on Zebrafish Embryo Revealed by Metabonomics
- 1. Key Laboratory for Yellow River and Huaihe River Water Environment and Pollution Control(Ministry of Education), Henan Key Laboratory of Environmental Pollution Control, College of Environment, Henan Normal University, Xinxiang 453007, China;
- 2. Key Laboratory of Pollution Processes and Environmental Criteria(Ministry of Education), Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China
- Received Date:
2019-01-07
Fund Project:
Abstract: Triphenyl phosphate (TPhP), a typical organophosphate flame retardant, is frequently detected in natural environment and organisms. In this study, the zebrafish were employed as model animal to explore the molecular mechanisms of the developmental toxicity of TPhP on aquatic animal. The zebrafish embryos were exposed to 0.0025, 0.1, 1, 10, 100 and 1 000 μg·L-1 TPhP solution from 2.5 hpf (hours post fertilization) to 7 dpf (days post fertilization), and the growths and mitochondrial function of zebrafish were investigated. The corresponding molecular mechanism was illuminated through metabolomics analysis. The results revealed that environmentally relevant concentrations (0.0025, 0.1, and 1 μg·L-1) of TPhP had no significant effects on the development of zebrafish embryo, but slightly disturbed the metabolism of zebrafish. By contrast, the heartbeat rates, hatching rates and mitochondrial membrane potential of zebrafish were decreased obviously when the concentrations of TPhP increased to 100 and 1 000 μg·L-1. The malformation rates increased by 6.8 and 12.5 times, and the mortality rates increased by 7.2 and 16.5 times, respectively. In addition, metabonomics analysis showed that metabolism of zebrafish were prominently affected in 10, 100 and 1 000 μg·L-1 TPhP-exposed treatments. Specifically, TPhP exposure inhibited amino acids metabolism by decreasing the levels of valine, leucine, isoleucine and inhibiting the aminoacyl-tRNA biosynthesis. The glucose glycolysis and tricarboxylic acid cycle were also inhibited. In conclusion, abnormal amino acids and glucose metabolism may be the main reasons for the developmental malformation of zebrafish induced by TPhP, and the disorder of tricarboxylic acid cycle was likely induced due to the mitochondrial dysfunction. These findings will provide new insights to the mechanisms of TPhP’s developmental toxicity.
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