Repeated administrations of Mn₃O₄ nanoparticles cause testis damage and fertility decrease through PPAR-signaling...

Potential health hazards of nanomaterials on male reproductive system have received raising concerns. Even though Mn₃O₄ nanoparticles (Mn₃O₄-NPs) is highly effective in clinical diagnostic and therapeutic applications of human disease, its potential toxic effect on the male reproductive system has not been reported. In this study, the testis damage and fertility decrease of male rats were conducted to testify the experimental reproductive injury induced by Mn₃O₄-NPs. After repeated tail vein injection with 10 mg/kg/week Mn₃O₄-NPs for 0, 60 and 120 days, Mn₃O₄-NPs accumulated in the testes resulted in oxidative stress and disorder of normal serum sex hormones. Experiments in vivo and in vitro indicated that mitochondria-mediated cell apoptosis were triggered via oxidative stress, demonstrated by the upregulation of malondialdehyde (MDA) and the depolarization of mitochondrial membrane potential. Notably, Mn₃O₄-NPs significantly resulted in a reduction of the quantity/quality of sperm and finally caused astonishing fertility decrease. Our preliminary result implied that the application of Mn₃O₄-NPs could be a double-edged sword and careful consideration should be given to the clinical uses.