Impact of copper nanoparticles (CuNPs) on hypothalamic GnRH and pituitary gonadotropins secretions in a male mouse: An immunohistochemical study

The copper nanoparticles (CuNPs) have widely been used for human welfare in the various applications. Despite its uses for beneficial purposes, CuNPs has been known to cause toxicity in the various organ based on the size, dose and duration. Both male and female reproductive functions have been to be compromised under CuNPs toxicity. The aim of this study is to investigate the effects of CuNPs after prolonged duration on the hypothalamus and pituitary in relation to the neuroendocrine regulation of reproduction in male mice since it has not been done before. Due to which the mice were orally treated with three doses of CuNPs viz. 10,100 and 200 mg/kg for 70 consecutive days to examines its adverse effects. The circulating GnRH levels and its abundance in the median eminence did not change in the CuNPs treated groups. However, circulating FSH showed significant decline in all the CuNPs treated groups, while LH was decline only in higher doses of CuNPs. The immunolocalization of LH and FSH also showed decreased abundance in the pituitary. Thus, pituitary function showed severely affected by CuNPs; the architecture of anterior pituitary also showed sign of degeneration such a presence of vacuoles and it was also shown that CuNPs treated groups have higher level of MDA which is an oxidative stress marker as indicated by the MDA staining. Moreover, the abundance of GnRHR and AR exhibited less abundance in the pituitary of higher dose of CuNPs treated groups. Thus, it can be concluded that pituitary becomes less responsive for hypothalamic GnRH and gonadal steroid, which could be reason of suppressed gonadotropin in the CuNPs treated mice.