生命周期暴露于环境相关浓度的磷酸二苯酯 (DPhP) 以性别特异性方式抑制斑马鱼的生长和能量代谢,Environmental Science & Technology

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生命周期暴露于环境相关浓度的磷酸二苯酯 (DPhP) 以性别特异性方式抑制斑马鱼的生长和能量代谢
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2021-09-15 , DOI: 10.1021/acs.est.1c03948
Qiliang Chen ₁ , Xiaolong Lian ₁ , Jingjing An ₁ , Ningbo Geng ₂ , Haijun Zhang ₂ , Jonathan K Challis ₃ , Yun Luo ₂ , Yaxin Liu ₄ , Guanyong Su ₄ , Yuwei Xie ₃ , Yingwen Li ₁ , Zhihao Liu ₁ , Yanjun Shen ₁ , John P Giesy _{3,

5,

6,

7} , Yufeng Gong ₃

Affiliation

由于磷酸芳基酯的商业用途和环境降解，磷酸二苯酯 (DPhP) 经常在环境基质中检测到，因此在世界范围内日益受到关注。然而，缺乏关于长期暴露于环境现实浓度的 DPhP 的潜在不利影响的信息。在这里，我们研究了生命周期暴露于 DPhP 对环境相关浓度 0.8、3.9 或 35.6 μg/L 的斑马鱼的影响，并采用双组学方法（代谢组学和转录组学）来表征潜在的作用模式。暴露于 35.6 μg/L 的 DPhP 120 天会导致雄性斑马鱼的体重和长度显着减少，但不会对雌性产生相同的影响。主要毒理学机制，包括抑制氧化磷酸化，集成双组学分析揭示了脂肪酸氧化的下调和磷脂酰胆碱降解的上调，并成功地与不良结果相关联。琥珀酸脱氢酶活性与肉碱蛋白质含量暴露于 DPhP 的雄鱼肝脏中O-棕榈酰转移酶 1 显着降低，这进一步证实了所提出的毒理学机制。这项研究首次证明，慢性、低水平的 DPhP 暴露可以通过抑制雄性斑马鱼的能量输出来延缓生长。

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Life Cycle Exposure to Environmentally Relevant Concentrations of Diphenyl Phosphate (DPhP) Inhibits Growth and Energy Metabolism of Zebrafish in a Sex-Specific Manner

Due to commercial uses and environmental degradation of aryl phosphate esters, diphenyl phosphate (DPhP) is frequently detected in environmental matrices and is thus of growing concern worldwide. However, information on potential adverse effects of chronic exposure to DPhP at environmentally realistic concentrations was lacking. Here, we investigated the effects of life cycle exposure to DPhP on zebrafish at environmentally relevant concentrations of 0.8, 3.9, or 35.6 μg/L and employed a dual-omics approach (metabolomics and transcriptomics) to characterize potential modes of action. Exposure to DPhP at 35.6 μg/L for 120 days resulted in significant reductions in body mass and length of male zebrafish, but did not cause those same effects to females. Predominant toxicological mechanisms, including inhibition of oxidative phosphorylation, down-regulation of fatty acid oxidation, and up-regulation of phosphatidylcholine degradation, were revealed by integrated dual-omics analysis and successfully linked to adverse outcomes. Activity of succinate dehydrogenase and protein content of carnitine O-palmitoyltransferase 1 were significantly decreased in livers of male fish exposed to DPhP, which further confirmed the proposed toxicological mechanisms. This study is the first to demonstrate that chronic, low-level exposure to DPhP can retard growth via inhibiting energy output in male zebrafish.

更新日期：2021-10-06

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