Treatment of copper nanoparticles (CuNPs) for two spermatogenic cycles impairs testicular activity via down-regulating steroid receptors and inhibition of germ cell proliferation in a mice model

Although copper is an indispensable trace metal for biological functions, its excess exposure causes hazardous effects on health. Copper in the form of nanoparticles (CuNPs) is widely used at present and therefore, the living organism is at continuous risk of its adverse effect. The prolonged treatment of CuNPs has not been evaluated yet on the male reproductive system. To demonstrate the combined adverse effects and the mechanism of copper nanoparticles (CuNPs), three doses of CuNPs, 10, 100 and 200 mg/kg were orally given to mice for 70 days. The present study demonstrated that CuNPs decreased the sperm quality parameters, male circulating hormones, induces testicular damages, increased oxidative stress, apoptosis, decreases antioxidant enzymes, germ cell proliferation, and increases the expression of 8-oxoguanine DNA glycosylase-1 (OGG1), apelin receptor (APJ) as well. CuNPs also down-regulated the expression of AR and Erα in the testis. These results suggest that CuNPs manifested their adverse effect on testis via modulating steroid and cytokine (apelin) receptors. The adverse effect of testis was most pronounced at the highest dose (200 mg/kg) of CuNPs, however, other doses show a less toxic effect on various parameters. In conclusion, results indicated that CuNPs may impair spermatogenesis via oxidative stress-mediated DNA damage and germ cell apoptosis at high doses.