Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China; School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China.
Environ Toxicol Pharmacol. 2022 May;92:103866. doi: 10.1016/j.etap.2022.103866. Epub 2022 Apr 27.
The herbicide glyphosate is being used worldwide. Hematological toxicity caused by glyphosate exposure has been reported, but the underlying mechanisms remain unclear. In this study, classical toxicology methods and RNA sequencing were performed to explore the molecular mechanisms related to glyphosate hematotoxicity. We found that 500 mg/kg b.w. glyphosate-based herbicide (GBH) significantly decreased leukocyte, neutrophil, lymphocyte and monocyte counts, as well as inhibited colony-forming abilities of CFU-GM, CFU-G and CFU-GEMM. RNA sequencing identified 82 and 48 differentially expressed genes (DEGs) in BM cells after treatment with 250 mg/kg and 500 mg/kg GBH, respectively. Meanwhile, GO and KEGG analyses revealed that the MAPK signaling pathway, hematopoietic cell lineage and cytokine-cytokine receptor interactions were vital pathways involved in GBH-induced toxicity in BM cells. Notably, Nr4a, Fos, Thbs1 and tnfrsf19 contributed to the hematotoxicity of GBH by regulating hematopoietic stem cell functions. In summary, our efforts enhance the understanding of the glyphosate hematotoxic responses and facilitate future studies on its corresponding mechanisms.
除草剂草甘膦正在全球范围内使用。已有报道称草甘膦暴露会引起血液毒性，但潜在机制仍不清楚。在这项研究中，我们采用经典毒理学方法和 RNA 测序技术，探索了与草甘膦血液毒性相关的分子机制。结果发现，500mg/kg 体重草甘膦基除草剂（GBH）显著降低了白细胞、中性粒细胞、淋巴细胞和单核细胞计数，并抑制了 CFU-GM、CFU-G 和 CFU-GEMM 的集落形成能力。RNA 测序结果显示，分别用 250mg/kg 和 500mg/kg GBH 处理后，BM 细胞中分别有 82 个和 48 个差异表达基因（DEGs）。同时，GO 和 KEGG 分析表明，MAPK 信号通路、造血细胞谱系和细胞因子-细胞因子受体相互作用是 GBH 诱导 BM 细胞毒性的重要途径。值得注意的是，Nr4a、Fos、Thbs1 和 tnfrsf19 通过调节造血干细胞功能，导致了 GBH 的血液毒性。综上所述，我们的研究工作增进了对草甘膦血液毒性反应的理解，并为进一步研究其相应机制提供了依据。
