J Environ Sci (China). 2026 Oct;168:392-399. doi: 10.1016/j.jes.2026.01.060. Epub 2026 Jan 27.
ABSTRACT
With the growing use of novel triazole fungicides, concerns over their toxicity and ecological effects have intensified. This study investigated the transgenerational cardiac toxicity of flusilazole (FLU) in zebrafish embryos and its underlying mechanisms. Fertilized eggs were exposed to 0.5, 1, or 2 μmol/L FLU, and larvae were reared in FLU-containing water until adulthood. These adults were then mated with unexposed fish to produce the F1 generation. The results showed that both F0 and F1 larvae developed cardiac arrhythmia and exhibited increased blood flow. Transcriptome profiling of F0 juveniles revealed significant enrichment in pathways governing cardiomyocyte development, differentiation, and apoptosis. In the hearts of both adult generations, the key cardiac function-related genes (nkx2.5, fli1, atp2al1, and atp2a2a) were upregulated, along with genes involved in cardiac development and calcium homeostasis, indicating impaired heart development. Importantly, cellular staining demonstrated that the decline in cardiac function was closely associated with enhanced apoptosis of cardiomyocytes. Furthermore, hereditary factors were shown to significantly contribute to the cardiac defects across generations. Overall, this study provides new mechanistic insights into pesticide-induced congenital heart disease, highlighting the role of apoptosis and gene dysregulation in transgenerational cardiac toxicity.
PMID:42680396 | DOI:10.1016/j.jes.2026.01.060