Intra-testicular injection of titanium dioxide nanoparticles induces chemical castration in male mice

Chemical castration has been widely studied as a less invasive alternative to surgical castration in male animals, primarily to induce sterility through azoospermia. This research investigates the potential of titanium dioxide nanoparticles (TiO₂ NPs) for chemical castration in male mice by administering intra-testicular injections and evaluating their efficacy through biochemical and histopathological changes. Fifty-six mice were divided into seven groups, including control, sham, and four experimental groups that received TiO₂ NPs at concentrations of 17.2, 34.45, 68.9, and 137.8 mg/mL, along with a surgical castration group. Over 33 days, we assessed sperm quality, testicular structure, oxidative stress markers, apoptosis-related gene expression, and fertility outcomes. TiO2 NPs significantly reduced sperm motility, viability, and plasma membrane functionality, while a decline in total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and Bcl-2 gene expression was observed. Histological alterations and reduced fertility indices were noted compared to controls. Conversely, TiO2 NP administration increased abnormal sperm morphology, DNA damage, malondialdehyde (MDA) levels, and Bax and caspase-3 gene expression. These findings suggest TiO2 NPs offer an efficient, minimally invasive, cost-effective approach to chemical castration, with potential applications in population control.