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世界范围内使用。草甘膦暴露引起的血液学毒性已有报道，但其潜在机制仍不清楚。本研究采用经典毒理学方法和RNA测序来探讨草甘膦血液毒性相关的分子机制。我们发现500 mg/kg体重的草甘膦除草剂（GBH）显着降低白细胞、中性粒细胞、淋巴细胞和单核细胞计数，并抑制CFU-GM、CFU-G和CFU-GEMM的集落形成能力。在用 250 mg/kg 和 500 mg/kg GBH 处理后，RNA 测序分别鉴定出 BM 细胞中的 82 个和 48 个差异表达基因 (DEG)。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诱导的BM细胞毒性的重要通路。值得注意的是，Nr4a、Fos、Thbs1 和 tnfrsf19 通过调节造血干细胞功能而导致 GBH 的血液毒性。总之，我们的努力增强了对草甘膦血液毒性反应的理解，并促进了对其相应机制的未来研究。