Environmentally relevant uranium exposure impairs spermatogenesis in goats through redox imbalance, blood-testis...

Uranium (U) contamination is a major environmental concern in uranium mining areas and nuclear-related contamination scenarios, yet its dose-associated reproductive toxicity in higher mammals remains poorly understood. Here, using male goats as a livestock-relevant mammalian model, we investigated the reproductive effects and mechanistic basis of 60-day graded uranium exposure. Uranium exposure caused pronounced testicular injury, characterized by seminiferous tubule atrophy, vacuolization, and germ cell sloughing, and promoted the accumulation of U in the testes (P < 0.05). These pathological changes were accompanied by increased sperm abnormalities and reduced sperm concentration, plasma membrane integrity, acrosome integrity, and mitochondrial activity (P < 0.05). Serum testosterone was significantly decreased, whereas luteinizing hormone and follicle-stimulating hormone were elevated (P < 0.01). Mechanistically, uranium exposure disrupted blood-testis barrier integrity, as evidenced by increased permeability and downregulation of ZO-1, Occludin, and Claudin (P < 0.01), and was further associated with aggravated oxidative stress, inflammatory activation, mitochondrial dysfunction, and apoptosis (P < 0.01). Integrated transcriptomic and metabolomic analyses revealed coordinated disturbances in steroidogenesis, lipid metabolism, and amino acid metabolism, together with repression of key genes involved in testosterone synthesis and spermatogenesis. These findings demonstrate that graded uranium exposure impairs testicular function and spermatogenesis through redox imbalance, endocrine disruption, and blood-testis barrier destruction, providing mechanistic insight into uranium chemotoxicity-induced reproductive impairment in herbivorous mammals.