Intratesticular copper oxide nanoparticles induce dose-dependent chemical castration in male mice

Chemical castration represents a non-surgical alternative to achieve male sterility by inducing azoospermia, with growing interest in nanoparticle-based agents owing to their targeted toxicity. This study aimed to determine whether intratesticular administration of copper oxide nanoparticles (CuO NPs) is effective in the chemical castration of male mice, and whether biochemical and histological changes can be assessed. Fifty-six adult male mice were divided into seven groups (n = 8 per group): a surgically castrated cohort, a control group, a sham group, and four experimental groups receiving CuO NPs at concentrations of 5, 10, 20, and 40 mg/mL. The assessment included fertility analysis after 30 days of treatment, sperm quality, testicular tissue, histological parameters, oxidative status, and gene expression. Testis weight, sperm parameters, and testosterone levels were significantly reduced by exposure to CuO NPs, but oxidative stress and DNA damage increased in a dose-dependent manner. Higher doses also decreased the expression of anti-apoptotic genes (Bcl-2) and increased that of pro-apoptotic genes (Bax and caspase-3). The correlation between these alterations and lower fertility indices highlighted the reproductive toxicity of CuO NPs. There were no noticeable differences between the control and sham groups for comparison. These findings suggest that intratesticular CuO NPs have potential as a method for chemical castration, offering a less invasive and more economical option for population-control applications.