Male reproductive toxicity induced by chronic dinotefuran exposure: In vivo and in silico evidence and the ameliorative role of Rosmarinus officinalis.

Dinotefuran (DINO), a chiral neonicotinoid insecticide, is widely used for pest control but increasing evidence suggests potential risks to non-target organisms, including mammals. This study evaluated the reproductive toxicity of chronic DINO exposure in male albino rats and assessed the ameliorative potential of Rosmarinus officinalis extract (RE). Male rats received DINO orally once daily at doses of 94 or 281 mg/kg for 25 consecutive weeks. DINO exposure impaired reproductive performance, as shown by significant reductions in the male mating and fertility indices, decreased testicular weight, and deterioration of sperm quality (count, motility, and viability), accompanied by increased sperm aneuploidy. Endocrine disruption was evident, with altered serum hormone profiles. Histopathological analysis revealed extensive testicular damage, and immunohistochemistry confirmed increased caspase-3 expression, reflecting enhanced apoptosis. Molecular docking supported these findings by demonstrating strong binding interactions of DINO with key enzymes and receptors involved in steroidogenesis and reproductive regulation (CYP11A1, CYP17A1, 3β-HSD, 17β-HSD, CYP19A1, caspase-3, AR, ERα/β, PRLR, TRα/β, FSHR, and LHCGR). Notably, co-treatment with RE (220 mg/kg) significantly alleviated these adverse effects, underscoring its antioxidant and ameliorative role. In conclusion, chronic DINO exposure poses substantial risks to male reproductive health, whereas RE demonstrates promising potential as a protective agent, particularly relevant in contexts of high pesticide exposure.