Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA214

Poster Communications

Gold and silver nanoparticles affect endocrine regulation of reproductive system in male rats

V. Kalynovskyi1, A. Pustovalov1, G. Grodzyuk2, N. Andrushina2, M. Dzerzhynsky1

1. Cytology, Histology and Reproductive Medicine Department, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine. 2. Nanomedtech-LLC, Kyiv, Ukraine.

Metallic nanoparticles are recognized as valuable agents used in different practical applications. However, their toxic properties are not fully understood (Lu et al., 2013). In vivo investigations of reproductive toxicity of nanometals often lead to controversial result (Ema et al., 2017; Jia et al., 2017). Thus, we estimated influence of gold and silver nanoparticles (nano-Au and nano-Ag, respectively) on the regulatory processes in the reproductive system of male rats. The experiment was conducted on the male albino rats Rattus norvegicus (two age groups; aged 1 and 6 month; n= 55 each). Experimental procedures lasted for 10 days. Nano-Au and nano-Ag (spherical, 8-12 nm average diameter) were injected intraperitoneally (i.p.) in the dose of 1 mg/kg . Stimulation and inhibition of reproductive system were achieved through 3µg/kg intracerebroventricular (i.c.v.) injections of kisspeptin-10 (Kp-10) and peptide-234 (P-234) respectively (Qureshi & Abbas, 2013). Intraperitoneal injections were made on days 1-10, i.c.v. - days 8-10. To perform i.c.v. injections, animals were anesthetized with a ketamine-xylazine solution (80mg/kg + 10 mg/kg i.m.). On the day 10, 1 hour post-injection, animals were sacrificed, their testicles and pituitaries taken and histologically processed. We measured cross-sectional area of Leydig cell's nuclei, as well as cross-sectional area of nuclei and cytoplasm of pituitary gonadotrophs. Also, we estimated testosterone (T) concentration in plasma. Means were compared using analysis of variance and Student's t-test. We found no significant changes in T concentration in younger, while in 6-month-old animals nano-Au and nano-Ag caused a 60% drop, comparing to controls. Kisspeptin-mediated stimulated stimulation was verified in both age groups. Kp-10 retained its stimulatory potential in combination with nanoparticles and T levels increased significantly: by 502% - 60,35±1,27 nmol/L vs 10,02±1,55 nmol/L (p<0.05, 6 month, nano-Au+Kp-10 vs nano-Au), 462% -57,23±1,73 nmol/L vs 10,17±1,14nmol/L (p<0.05, 6 month, nano-Ag+Kp-10 vs nano-Ag), 586% - 33,97±20,80 nmol/L vs 4,95±0,44 nmol/L (p<0.05,1 month, nano-Au+Kp-10 vs nano-Au), and 398% - 21,82±3,24 nmol/L vs 4,38±0,43 nmol/L (p<0.05,1 month, nano-Ag+Kp-10 va nano-Ag). However, no supporting increase in Leydig cell's nuclei cross-sectional area was found. Injections of P-234 (combined and solely) caused significant drop of T levels in 6-month-old animals only. Nanoparticle-induced decrease in testicular activity was not supported by findings in pituitary. In contrary to expected increase in pituitary activity due to the realization of negative feedback, we found downregulation of gonadotrophs by both types of nanometals. Therefore, nanoparticles disrupt endocrine regulatory networks in reproductive system of rats, although exact mechanisms are still to be estimated.

Where applicable, experiments conform with Society ethical requirements