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

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

  • Environ Sci Technol. 2021 Oct 5;55(19):13122-13131. 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
Affiliations

Affiliations

  • 1 Chongqing Key Laboratory of Animal Biology, School of Life Sciences, Chongqing Normal University, Chongqing 401331, China.
  • 2 CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, Liaoning, China.
  • 3 Toxicology Centre, University of Saskatchewan, Saskatoon S7N 5B3, SK, Canada.
  • 4 School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, Jiangsu, China.
  • 5 Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon S7N 5B4, SK, Canada.
  • 6 Department of Environmental Sciences, Baylor University, Waco, Texas 76798-7266, United States.
  • 7 State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, Jiangsu, China.
PMID: 34523920 DOI: 10.1021/acs.est.1c03948
Abstract

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.

Keywords

diphenyl phosphate; fatty acid oxidation; gene set enrichment analysis (GSEA); metabolomics; oxidative phosphorylation; transcriptomics.

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