Hematopoietic stem cell and immunotoxicity in zebrafish embryos induced by exposure to Metalaxyl-M

Abstract Metalaxyl-M (MM), a protective and therapeutic fungicide, has been shown to be a promising candidate, but its toxicity toward aquatic organisms is unknown. In this study, we evaluated for the first time the immunotoxicity of MM in zebrafish embryos. Phenotypes (heart rate, body length, and yolk area) and the number of neutrophils, macrophages, and T cells in the thymus were analyzed in zebrafish embryo after exposure to MM. Our results showed that zebrafish embryos exposed to MM showed a concentration-dependent increase in the yolk area and a significant decrease in the number of neutrophils, macrophages, and thymus T cells. We detected upregulated expression of related immune signaling genes, such as tnfa, nfkb3, cxcl-c1c, il6, mmp9, and tgfb1. Additionally, we observed a significant decrease in HSCs in zebrafish larvae after exposure to MM. IWR-1 could restore the number of neutrophils and macrophages after exposure to MM. The results indicated that MM exerted developmental toxicity and immunotoxicity to zebrafish embryos, and these phenomena may be caused by MM's regulation of WNT signaling pathway.