PFDoA induces developmental and immune toxicity in zebrafish through ROS-mediated inflammation-apoptosis signaling.

Abstract

Perfluorododecanoic acid (PFDoA) is a persistent and bioaccumulative long-chain perfluoroalkyl acid, yet the mechanisms underlying its immunotoxicity remain poorly understood. This study investigated PFDoA-induced immunotoxicity in zebrafish embryos, demonstrating that 72 h exposure caused dose-dependent developmental toxicity (reduced survival, bradycardia, and shortened body length), markedly decreased neutrophil and macrophage populations, and induced thymic atrophy, indicating impairment of both innate and adaptive immunity. Transcriptomic analysis revealed enrichment of PPAR signaling, apoptosis, and fatty acid metabolism pathways; qPCR confirmed upregulation of pro-inflammatory cytokines (CXCL-C1C, TNF-α, IL-1β) and apoptosis-related genes (p53), along with downregulation of antioxidant genes and Bcl-2/Bax ratio. PFDoA also elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreased superoxide dismutase (SOD) activity, but increased catalase (CAT) activity. Co-exposure to the antioxidant astaxanthin (ATX) partially rescued PFDoA-induced immune cell loss. Collectively, these findings demonstrate that PFDoA disrupts immune development in zebrafish embryos by triggering an ROS-mediated inflammation-apoptosis axis, providing mechanistic insight into the immunotoxicity of long-chain perfluoroalkyl acids and highlighting antioxidant intervention as a potential mitigating strategy.