Hematological effects of glyphosate in mice revealed by traditional toxicology and transcriptome sequencing

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 CFUGEMM. 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.

Automated summary

In this study, the molecular mechanisms underlying glyphosate-induced hematotoxicity were explored using classical toxicology methods and RNA sequencing. The results showed that glyphosate-based herbicide significantly decreased leukocyte, neutrophil, lymphocyte and monocyte counts, as well as inhibited colony-forming abilities of hematopoietic stem cells. The MAPK signaling pathway, hematopoietic cell lineage, and cytokine-cytokine receptor interactions were identified as vital pathways involved in glyphosate-induced toxicity in bone marrow cells.