Alterations In Reproductive Parameters And Gene Expression In Murine Male Testis After Exposure To Silver Nanoparticles (AgNPs)

Nanotechnology has been an ever expanding area of research and opportunities during the recent years. Due to the novel physical and chemical properties of materials on the nanoscale, nanomaterials have been used to create new consumer products as well as applications for life sciences and biotechnology. Chemically, the nanoparticles(NPs) are very diverse. It is estimated that of all the nanomaterials used in consumer products, silver(Ag) NPs currently have the highest degree of commercialization. Monovalent silver compounds, especially silver nitrate, have been used extensively for antimicrobial treatment. These antimicrobial properties are retained in AgNPs and exploited in e.g. nanofiber mats, bandages, wound dressings and ointments. Additionally, AgNPs have been used to prevent bacterial colonization on various surfaces such as catheters, prostheses and clothing. Thus, humans can be exposed to AgNPs from many different sources. Despite the increasing use of AgNPs in commercial products, there is a serious lack of information concerning the toxicity and cellular responses to AgNPs.Previous studies about the toxicity of silver nanoparticles mainly focused on in vitro experiments which investigated on monocytes, spermatogonial stem cells, human spermatozoo, lung fibroblasts, murine embryonic stem cells, etc. However, there are limited in vivo experiments, including Effects of prepubertal exposure to silver nanoparticles on reproductive parameters in adult male Wistar rats, exposure to silver nanoparticles on liver in rats or on respiratory system via inhalation administration. Thus, this study aimed to investigate the effects of silver nanoparticles on mice male reproductive system by oral administration for 90 days.Objective:This study aimed to investigate the toxic effects of AgNPs on male reproductive system and the possible mechanisms based on gene expression.Methods:We exposed Balb/c male mice of 6-weeks to AgNPs daily [0(control), 30 or 125 mg/kg.BW] for 90 days. The effects on testis histological structure, sperm production,cellular apoptosis in testis tissues and the levels of fertility-associated hormones were measured. Differentially expressed genes were identified by microarray analysis, and dysregulated protein expression was verified by immunofluorescence and western-blotting.Results:Our results indicated that 125 mg/kg AgNPs exposure caused changes in testis histology, sperm count and cellular apoptosis in the testis. However, the testis index and concentrations of follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone were not changed markedly among different groups. Microarray analysis showed that 383 genes were significantly altered in testis from mice treated by 125 mg/kg AgNP groups as compared to the controls, theses altered genes were associated with apoptosis, oxidative stress and other signaling pathways. Furthermore, the increased expression of apoptosis-related molecules(caspase 3, Myc and Mdm2) may explain the high levels of apoptosis in the testis after 125 mg/kg AgNPs exposure.Conclusion:These results demonstrated that AgNPs evoked detrimental changes in male reproductive system by modulating apoptosis-related genes. Our findings provided an explanation for the toxicity of AgNPs to male reproductive system, and highlighted the safe use of AgNPs.