Chronic glyphosate exposure compromises male reproductive health: Golgi dysfunction mediating spermatogenesis impairment.

Growing evidence links global male infertility to environmental endocrine disruptors, particularly pesticides. As the world's most extensively used herbicide, glyphosate (GLY) poses significant concerns for human reproductive health. While epidemiological studies suggest associations between GLY exposure and male infertility, conclusive evidence elucidating its reproductive toxicity remains limited and controversial. Thus, this study established an 18-week rat model of chronic GLY exposure to investigate its impact on male reproductive health. Data demonstrated that chronic dietary exposure to GLY reduced sperm quality and impaired acrosome integrity. Transcriptomic analysis revealed that GLY impairs sperm acrosome by disrupting acrosome assembly. Ultrastructural pathology and immunofluorescence observations further indicated that GLY disrupted acrosome biogenesis by reducing the accumulation and fusion of golgi associated PDZ and coiled-coil motif containing (GOPC)-decorated proacrosomal vesicles. Mechanistically, oxidative stress-mediated Golgi damage was identified as the primary driver of GLY-impaired proacrosomal vesicle release. Significantly, GLY-induced Golgi damage and the resultant sperm acrosomal malformation were effectively mitigated by supplementing with the antioxidant puerarin. Collectively, this study first establishes a mechanistic link between Golgi apparatus dysfunction and defective acrosome formation, underscoring redox imbalance as a pivotal mediator of GLY-induced reproductive toxicity. These findings provide novel mechanistic insights into environmental pollutant-driven oxidative stress as a risk factor for male reproductive health.