4-octylphenol (4-OP), a toxic estrogenic environmental pollutant, can threaten aquatic animal and human health. However, toxic effect of 4-OP on fish has not been reported. To investigate molecular mechanism of gill poisoning caused by 4-OP exposure, a carp 4-OP poisoning model was established, and then blood and gills were collected on day 60. The results demonstrated that gill was a target organ attacked by 4-OP, and exposure to 4-OP caused carp gill inflammatory injury. There were 1605 differentially expressed genes (DEGs, including 898 up-regulated DEGs and 707 down-regulated DEGs). KEGG and GO were used to further analyze obtained 1605 DEGs, indicating that complement activation, immune response, and inflammatory response participated in the mechanism of 4-OP-caused carp gill inflammatory injury. Our data at transcription level further revealed that 4-OP caused complement activation through triggering complement component 3a/complement component 3a receptor (C3a/C3aR) axis and complement component 5a/complement component 5a receptor 1 (C5a/C5aR1) axis, induced immunosuppression through the imbalances of T helper (Th) 1/Th2 cells and regulatory T (Treg)/Th17 cells, as well as caused inflammatory injury via toll like receptor 7/inhibitor kappa B alpha/nuclear factor-kappa B (TLR7/IκBα/NF-κB) pathway. Taken together, immunosuppression participated in complement activation-mediated inflammatory damage in carp gills after 4-OP treatment. The findings of this study will provide pioneering information and theoretical support for the mechanism of 4-OP poisoning, and will provide reference for the assessment of estrogenic environmental pollution risk.

4-辛基苯酚 (4-OP) 是一种有毒的雌激素环境污染物，可威胁水生动物和人类健康。然而，尚未报道 4-OP 对鱼类的毒性作用。为探讨4-OP暴露引起鳃中毒的分子机制，建立鲤鱼4-OP中毒模型，在第60天采集血液和鳃。结果表明，鳃是4-OP攻击的靶器官，并且暴露于4-OP引起鲤鱼鳃炎性损伤。有1605个差异表达基因（DEGs，包括898个上调的DEGs和707个下调的DEGs）。用KEGG和GO对获得的1605个DEGs进行进一步分析，表明补体激活、免疫反应和炎症反应参与了4-OP致鲤鱼鳃炎性损伤的机制。我们在转录水平的数据进一步表明，4-OP 通过触发补体成分 3a/补体成分 3a 受体 (C3a/C3aR) 轴和补体成分 5a/补体成分 5a 受体 1 (C5a/C5aR1) 轴引起补体激活，通过诱导免疫抑制T辅助（Th）1/Th2细胞和调节性T（Treg）/Th17细胞失衡，以及通过toll样受体7/抑制剂κBα/核因子-κB（TLR7/IκBα/NF）引起炎症损伤-κB) 途径。总之，免疫抑制参与了 4-OP 治疗后鲤鱼鳃中补体激活介导的炎症损伤。本研究结果将为 4-OP 中毒机制提供开创性的信息和理论支持，