Kisspeptin-mediated regulation of testicular activity of rats under the effect of gold nanoparticles

Abstract

There are a variety of biomedical applications of nanoparticles. They can be used as drug carriers, anti-tumor agents, biosensors and modulators of immune response. But full-scale real clinical application of nanomaterials requires a great deal of information on their safety and biotoxicity. Even traditionally harmless materials, like gold, can obtain toxic features when scaled to the nanosize. In vitro studies showed that nanoparticles can be geno- and cytotoxic, but their effects on the body as a whole remain largely a mystery. To shed some light on this, our study focused on the reproductive toxicity of nanomaterials. We synthesized 10–15 nm gold nanoparticles through the reduction of sodium tetrachloroaurate (III) in an alkaline medium with the addition of sodium polyphosphate as a stabilizing agent. Next, these particles were administered intraperitoneally to young and old rats for 10 days. To test functional capabilities of the testes, we injected kisspeptin-10 or its antagonist peptide-234 intracerebroventricularly. These substances are known to stimulate or inhibit the central component of the hypothalamic-pituitary-gonadal axis respectively. After the routine histological procedures, we measured the diameter of seminiferous tubules and the nuclear cross-sectional area of Sertoli cells as markers of testicular spermatogenic activity and a cross-sectional area of the Leydig cells’ nuclei as a marker of testicular steroidogenesis. We found that injections of nanogold caused no significant changes in the young animals. At the same time, morphometric parameters of adult animals were significantly lower compared to control, although we observed no pathological changes in the tissue. Combined administration of gold nanoparticles and kisspeptin showed that the stimulatory effect of the latter was not observed at all. This is a specific feature of toxicants called “endocrine disruptors”. Moreover, we found morphological signs of testicular degeneration, which are characteristic of the low-testosterone state. Simultaneous injections of gold and peptide-234 resulted in the highest degree of testicular functional downregulation, regardless of age. Taken as a whole, our data indicates that gold nanoparticles disrupt the regulatory network of the hypothalamic-pituitary-gonadal axis, possibly due to direct action on the interstitial cells and spermatogenic epithelium.

Keywords

• nanogold
• Sertoli cells
• Leydig cells
• kisspeptin-10
• peptide-234