Low‐Dose Glyphosate‐Based Herbicide Exposure Induces Oxidative Stress and Impairs Hormonal and Reproductive Function in Male Rats

Roundup is a glyphosate-based herbicide (GBH) widely used for weed control. Because it targets a pathway absent in animals, it has long been considered to have minimal effects on animal health. However, increasing evidence suggests potential reproductive toxicity. We investigated the effects of low-level exposure to a GBH in adult male Sprague Dawley rats (8-9 weeks old), administered orally via tap water for 30 days, corresponding to microgram-level glyphosate-equivalent exposure. We evaluated sperm parameters, reproductive organ weights, fertility outcomes, circulating hormones, and testicular oxidative stress markers. Estimated daily GBH (glyphosate-equivalent) intakes were 55 μg/kg/day (0.7 mg/L) and approximately 6 mg/kg/day (70 mg/L). Both exposure levels reduced male fertility, evidenced by increased embryonic resorptions in females mated with treated males. High-dose exposure reduced testicular and epididymal weights, whereas low-dose exposure decreased prostate weight. Sperm counts and daily sperm production were significantly reduced at both doses, with increased abnormal sperm morphology, indicating impaired fertilization potential. Hormonal analysis showed dose-dependent disruption of the hypothalamic-pituitary-gonadal axis. Testosterone and luteinizing hormone were reduced at the higher dose, whereas estradiol increased, and follicle-stimulating hormone decreased at the lower dose. In testicular tissue, low-dose GBH exposure enhanced antioxidant activity, whereas higher exposure suppressed key antioxidant enzymes and increased lipid peroxidation, indicating oxidative stress. Overall, even very low concentrations of GBH altered male reproductive function through disrupting hormonal balance, impairing sperm quality, and inducing oxidative stress in the testes. These findings suggest that exposure levels considered safe may still pose risks to male reproductive health.