Procymidone induces muscle atrophy and impaired myocyte fusion via the TNF-α/NF-κB/ROS pathway in developing zebrafish embryos.

Procymidone (PCM), a fungicide widely used to control gray mold and Sclerotinia rot in agricultural production, is known for its hepatotoxic and endocrine-disrupting effects; however, its potential myotoxicity remains largely unexplored. To evaluate muscle toxicity and underlying mechanisms, zebrafish embryos were exposed to PCM (1, 1.25, 1.5 mg/L) until 72 h post-fertilization (hpf). Transgenic models revealed that PCM exposure was associated with myopathic phenotypes, including muscle atrophy and aberrant muscle cell fusion. Transcriptomic analysis identified extensive dysregulation of genes involved in muscle development, differentiation, fusion, and motor function. PCM exposure was accompanied by increased reactive oxygen species (ROS) levels and elevated apoptosis in affected tissues. Gene Set Enrichment Analysis (GSEA) suggested enrichment of Toll-like receptor and apoptosis signaling pathways, which have been associated with muscle atrophy. Integrative analyses suggested that PCM-induced muscular toxicity is associated with coordinated alterations in TNF-α/NF-κB signaling and oxidative stress. Notably, co-treatment with an NF-κB inhibitor partially alleviated PCM-induced muscle atrophy. Together, these findings indicate that PCM exposure induces muscular toxicity in developing zebrafish, which is associated with oxidative stress and inflammation-related apoptotic responses. This study provides mechanistic insight into procymidone-associated skeletal muscle toxicity and contributes to the understanding of its potential impacts on aquatic organisms.