Spermatogenic cell apoptosis and impaired spermatogenesis in prepubertal mice: time- and dose-dependent toxicity of silver nanoparticles.

Context The increasing use of nanoparticles (NPs) in various consumer, agricultural, and pharmaceutical applications has raised considerable concern about their potential risks to human health and the environment. Aims This study investigated the progressive toxic effects of silver nanoparticles (AgNPs) in mouse testes after single and repeated exposure. Methods Prepubertal male mice were exposed to AgNPs by gavage at 50, 200, and 500mg/kg body weight. Testis, epididymis, and serum were collected and subjected to histopathological analysis. Key results Daily exposure to AgNPs for 7 and 15days (n =8) decreased sperm count, while increasing abnormal sperm count and testicular atrophy in a dose- and exposure-time-dependent manner. A single exposure to AgNPs at a dose of 200mg/kg body weight (n =8) resulted in testicular histopathological changes and spermatogenic cell apoptosis in a time-dependent manner. The highest number of apoptotic cells was detected 24h after exposure, whereas testicular testosterone (TT) concentrations decreased at 12 and 24h. To explore whether AgNPs suppress TT concentrations by affecting the hypothalamus-pituitary-testicular (HPT) axis, we analyzed serum LH concentrations; however, no significant changes in LH levels were found. Conclusion This study showed that AgNPs cause potential adverse effects on the testis, specifically, spermatogenic cell apoptosis, and impaired spermatogenesis in an exposure time- and dose-dependent manner. The testicular toxicity was not associated with suppression of the HPT axis, possibly involving other mechanisms. Implications These findings contribute to the broader discussion on NP safety and regulatory considerations, particularly regarding their reproductive toxicity.