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Published on: November 30, 2017
Hematopoietic stem cell and immunotoxicity in zebrafish embryos induced by exposure to Metalaxyl-M
Suwen Zeng1, Yuyang Peng1, Jinze Ma1
1Ganzhou Cancer Hospital-Gannan Normal School Joint Research Center for Cancer Prevention and Treatment, Ganzhou Key Laboratory for Drug Screening and Discovery, Gannan Normal University, Ganzhou, 341000, Jiangxi, China.
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.
Insights
Metalaxyl-M fungicide causes developmental and immune toxicity in zebrafish embryos by affecting immune cell counts and gene expression. The WNT signaling pathway may be involved in these toxic effects.
Area of Science:
- Environmental toxicology
- Immunology
- Developmental biology
Background:
- Metalaxyl-M (MM) is a widely used fungicide with unknown aquatic toxicity.
- Zebrafish embryos are a valuable model for studying developmental and immune toxicity.
Purpose of the Study:
- To evaluate the immunotoxicity of Metalaxyl-M (MM) in zebrafish embryos.
- To investigate the effects of MM on immune cell populations and gene expression.
- To explore the potential role of the WNT signaling pathway in MM-induced toxicity.
Main Methods:
- Zebrafish embryos were exposed to varying concentrations of MM.
- Phenotypic assessments included heart rate, body length, and yolk area.
- Immune cell counts (neutrophils, macrophages, T cells, HSCs) were quantified.
- Expression levels of immune signaling genes were analyzed.
- The effect of IWR-1 on MM-induced toxicity was assessed.
Main Results:
- MM exposure led to a concentration-dependent increase in yolk area and decreased body length.
- Significant reductions in neutrophils, macrophages, thymus T cells, and HSCs were observed.
- Upregulated expression of immune-related genes (tnfa, nfkb3, cxcl-c1c, il6, mmp9, tgfb1) was detected.
- IWR-1 treatment partially restored neutrophil and macrophage numbers.
Conclusions:
- Metalaxyl-M exhibits developmental and immunotoxicity in zebrafish embryos.
- MM exposure impacts immune cell development and function.
- WNT signaling pathway dysregulation may underlie MM's toxic effects.
- Further research is needed to fully elucidate the mechanisms of MM toxicity.
