Melatonin attenuates reproductive toxicity of prothioconazole and its metabolite via spermatogenesis and oxidative stress

Prothioconazole (PTC), a widely used triazole fungicide, and its metabolite, prothioconazole-desthio (dPTC), have been frequently detected in environmental matrices, raising significant concerns regarding their potential adverse effects on mammalian reproductive health. While melatonin has demonstrated protective properties across multiple physiological systems, its efficacy in mitigating PTC- and dPTC-induced reproductive toxicity remains poorly understood. This study investigated the reproductive effects of PTC and dPTC in male mice and evaluated the potential protective effects of melatonin. PTC and dPTC exposure induced reproductive dysfunction, characterized by reduced sperm counts, disrupted spermatogenesis, altered HPG axis hormone secretion, elevated oxidative stress, and compromised BTB integrity. Melatonin co-treatment significantly attenuated these adverse effects, restoring sperm parameters, normalizing HPG axis function, mitigating oxidative stress, and preserving BTB integrity, possibly via the modulation of the MAPK/ERK signaling pathway. These findings underscore the potential reproductive toxicity of PTC/dPTC and propose melatonin as a promising therapeutic approach to alleviate the adverse reproductive impacts induced by triazole fungicides.