Xiao Juhua, Yang Dou, Hu Boxi, Zha Wenwen, Li Weirong, Wang Ying, Liu Fasheng, Liao Xinjun, Li Huimin, Tao Qiang, Zhang Shouhua, Cao Zigang
Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, 330006, Jiangxi, China.
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2025 Jan;287:110037. doi: 10.1016/j.cbpc.2024.110037. Epub 2024 Sep 7.
Several studies reported that the widespread use of perfluoroalkyl and polyfluoroalkyl substances (PFASs) causes increased environmental pollution, subsequently impacting aquatic organisms. Perfluoroalkyl substances such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) reportedly cause cardiotoxicity, neurotoxicity, and developmental toxicity in different organisms. However, whether perfluorodecanoic acid (PFDA), a widely used perfluoroalkyl substance, induces animal embryos developmental toxicity remain unknown. Here, we explored the immunotoxicity and associated mechanisms of PFDA in zebrafish embryos via RNA sequencing, morphological assessment and behavioral alteration detection following exposure to 0.5, 1 and 2 mg/L of PFDA. Interestingly, We found that with the increase of PFDA to drug concentration, including neutrophils and macrophages, significantly increased the number of inherent cells, immune related genes expression. Furthermore, oxidative stress increased in the PFDA-treated embryos in a dose-dependent manner and inhibition of oxidative stress levels effectively rescued the number of neutrophils. Changes in embryonic behavior were observed after exposure to PFDA. Overall, our results suggest that PFDA may induce innate immune response by accumulation of oxidative stress in zebrafish at early developmental stages, and concern is needed about its environmental exposure risks for animals embryos development. ENVIRONMENTAL IMPLICATION: Perfluorinated and polyfluorinated alkyl substances (PFASs) are a class of synthetic organic compounds containing fluorine widely used as lubricants, surfactants, insecticides, etc. The PFDA, a typical perfluorinated compound, is often used as a wetting agent and flame retardant in industries. Several studies showed that PFASs can cause serious environmental pollution, leading to developmental toxicity to various animals, including reproductive toxicity, liver toxicity, heart toxicity, neurotoxicity, and immunotoxicity. However, there are still limited studies on the effects and mechanisms of PFDA on aquatic organisms. Therefore, there is a need to evaluate the ecological risks of PFDA in animals.
多项研究报告称，全氟烷基和多氟烷基物质（PFASs）的广泛使用导致环境污染加剧，进而影响水生生物。据报道，全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）等全氟烷基物质会在不同生物体内引发心脏毒性、神经毒性和发育毒性。然而，广泛使用的全氟烷基物质全氟癸酸（PFDA）是否会诱导动物胚胎发育毒性仍不清楚。在此，我们通过RNA测序、形态学评估以及在暴露于0.5、1和2mg/L的PFDA后检测行为改变，探究了PFDA对斑马鱼胚胎的免疫毒性及相关机制。有趣的是，我们发现随着PFDA药物浓度的增加，包括中性粒细胞和巨噬细胞在内的固有细胞数量显著增加，免疫相关基因表达上调。此外，PFDA处理的胚胎中氧化应激以剂量依赖的方式增加，抑制氧化应激水平可有效挽救中性粒细胞数量。暴露于PFDA后观察到胚胎行为发生变化。总体而言，我们的结果表明，PFDA可能通过在斑马鱼早期发育阶段积累氧化应激来诱导先天免疫反应，其对动物胚胎发育的环境暴露风险值得关注。环境影响：全氟和多氟烷基物质（PFASs）是一类含氟的合成有机化合物，广泛用作润滑剂、表面活性剂、杀虫剂等。典型的全氟化合物PFDA在工业中常被用作湿润剂和阻燃剂。多项研究表明，PFASs会造成严重的环境污染，对包括生殖毒性、肝脏毒性、心脏毒性、神经毒性和免疫毒性在内的各种动物产生发育毒性。然而，关于PFDA对水生生物影响及机制的研究仍然有限。因此，有必要评估PFDA在动物中的生态风险。
