Integrated metabolomics and transcriptomics reveal glyphosate based‐herbicide induced reproductive toxicity through disturbing energy and nucleotide metabolism in mice testes

Abstract

AbstractGlyphosate is a widely used herbicide that has deleterious effects on animal reproduction. However, details regarding the systematic mechanisms of glyphosate‐induced reproductive toxicity are limited. This study aimed to investigate the toxic effects of glyphosate‐based herbicide (GBH) on reproduction in mice exposed to 0 (control group), 50 (low‐dose group), 250 (middle‐dose group), and 500 (high‐dose group) mg/kg/day GBH for 30 days. Toxicological parameters, metabolomics, and transcriptomics were performed to reveal GBH‐induced reproductive toxicity. Our findings demonstrated that GBH exposure damaged mitochondrial pyknosis and the nuclear membrane of spermatogonia. GBH triggered a significant increase in sperm malformations in the high‐dose group. Omics data showed that GBH impaired the Krebs cycle and respiratory chain, blocked pyruvate metabolism and glycolysis/gluconeogenesis, and influenced the pentose phosphate pathway and nucleotide synthesis and metabolism. Overall, the multi‐omics results revealed systematic and comprehensive evidence of the adverse effects of GBH exposure, providing new insights into the reproductive toxicity of organophosphorus pesticides.