Yang Zhiyi, Fu Lei, Cao Mengxi, Li Fang, Li Jingguang, Chen Zhiyu, Guo Ang, Zhong Huifang, Li Wenbo, Liang Yong, Luo Qian
Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Institute of Environment and Health, Jianghan University, Wuhan 430056, China.
Sci Total Environ. 2023 Feb 25;861:160691. doi: 10.1016/j.scitotenv.2022.160691. Epub 2022 Dec 5.
Per- and polyfluoroalkyl substances (PFASs) are persistent environmental contaminants, posing developmental toxicity to fish and human. PFAS-induced lipid metabolism disorders were demonstrated using the zebrafish (Danio rerio) embryo model, but the detailed changes of lipid compositions and the influence of these changes on the biological development are still unclear. Herein, lipidomics analysis was performed to reveal the dysregulations of lipid metabolism in zebrafish embryos exposed to perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) through microinjection. Various abnormal phenotypes were observed, including heart bleeding, pericardium edema, spinal curvature and increased heart rate at 72 h after fertilization, especially in the PFOS exposure groups. Lipidomic profiling found downregulated phosphatidylethanolamines in the PFAS-exposed embryos, especially those containing a docosahexaenoyl (DHA) chain, indicating an excessive oxidative damage to the embryos. Glycerolipids were mainly upregulated in the PFOA groups but downregulated in the PFOS groups. These aberrations may reflect oxidative stress, energy metabolism malfunction and proinflammatory signals induced by PFASs. However, supplement of DHA may not be effective in recovering the lipidomic dysregulations and protecting from the developmental toxicity induced by PFASs, showing the complexity of the toxicological mechanisms. This work has revealed the associations between the abnormal phenotypes and dysregulations of lipid metabolism in zebrafish embryos induced by PFASs from the aspect of lipidomics, and discovered the underlying molecular mechanisms of the developmental toxicity of PFASs.
全氟和多氟烷基物质（PFASs）是持久性环境污染物，对鱼类和人类具有发育毒性。使用斑马鱼（Danio rerio）胚胎模型证明了PFASs诱导的脂质代谢紊乱，但脂质组成的详细变化以及这些变化对生物发育的影响仍不清楚。在此，通过微量注射对暴露于全氟辛酸（PFOA）或全氟辛烷磺酸（PFOS）的斑马鱼胚胎进行脂质组学分析，以揭示脂质代谢的失调。观察到各种异常表型，包括受精后72小时出现心脏出血、心包水肿、脊柱弯曲和心率增加，尤其是在PFOS暴露组中。脂质组学分析发现，暴露于PFASs的胚胎中磷脂酰乙醇胺下调，尤其是那些含有二十二碳六烯酰（DHA）链的磷脂酰乙醇胺，表明胚胎受到过度氧化损伤。甘油脂在PFOA组中主要上调，但在PFOS组中下调。这些异常可能反映了PFASs诱导的氧化应激、能量代谢功能障碍和促炎信号。然而，补充DHA可能无法有效恢复脂质组学失调并防止PFASs诱导的发育毒性，这表明毒理学机制的复杂性。这项工作从脂质组学的角度揭示了PFASs诱导的斑马鱼胚胎异常表型与脂质代谢失调之间的关联，并发现了PFASs发育毒性的潜在分子机制。
