Abstract
Zinc Oxide Nanoparticles (ZnO NPs) are a type of metal oxide nanoparticle with an extensive use in biomedicine. Several studies have focused on the biosafety of ZnO NPs, since their size and surface area favor entrance and accumulation in the body, which can induce toxic effects. In previous studies, ZnO NPs have been identified as a dose- and time-dependent cytotoxic inducer in testis and male germ cells. However, the consequences for the first cell stage of spermatogenesis, spermatogonia, have never been evaluated. Therefore, the aim of the present work is to evaluate in vitro the cytotoxic effects of ZnO NPs in spermatogonia cells, focusing on changes in cytoskeleton and nucleoskeleton. For that purpose, GC-1 cell line derived from mouse testes was selected as a model of spermatogenesis. These cells were treated with different doses of ZnO NPs for 6 h and 12 h. The impact of GC-1 cells exposure to ZnO NPs on cell viability, cell damage, and cytoskeleton and nucleoskeleton dynamics was assessed. Our results clearly indicate that higher concentrations of ZnO NPs have a cytotoxic effect in GC-1 cells, leading to an increase of intracellular Reactive Oxygen Species (ROS) levels, DNA damage, cytoskeleton and nucleoskeleton dynamics alterations, and consequently cell death. In conclusion, it is here reported for the first time that ZnO NPs induce cytotoxic effects, including changes in cytoskeleton and nucleoskeleton in mouse spermatogonia cells, which may compromise the progression of spermatogenesis in a time- and dose-dependent manner.
Highlights
ZnO Nanoparticles (ZnO NPs) have numerous applications due to their exceptional set of physicochemical properties, making them suitable for several biomedical applications, such as drug delivery system, bioimaging, molecular diagnostics, and cancer therapy [1,2,3]
20 μg/mL of ZnO NPs, GC-1 viability did not significantly decrease after 12 h of ZnO NPs exposure. These results indicate that ZnO NPs concentrations lower than 20 μg/mL were not enough to induce negative and permanent impact in spermatogonia cells once GC-1 can recover from toxic effects of
The present study describes for the first time the cytotoxic effects of ZnO NPs on spermatogonia cells (GC-1) in a time- and dose-dependent manner
Summary
ZnO Nanoparticles (ZnO NPs) have numerous applications due to their exceptional set of physicochemical properties, making them suitable for several biomedical applications, such as drug delivery system, bioimaging, molecular diagnostics, and cancer therapy [1,2,3]. Considering the wide range of applications and the high human exposure to ZnO NPs, the biosafety studies of these NPs are even more imperative, given that the principal applications focus on. Cells 2020, 9, 1081 in vivo exposure of ZnO NPs, either orally, intratracheally, or by inhalation, leads to easy accumulation in several tissues and that the rate of accumulation depends on the tissue. Kidney, lung, brain, and spleen are vital organs with high levels of ZnO accumulation [9], presenting signs of cytotoxicity as a consequence of exposure and accumulation of ZnO NPs [10,11,12,13]. Metal nanoparticles have the capacity to cross the blood–testis barrier (BTB), in part due to their size and by the generation of inflammatory response compromising the integrity of BTB [8]. It is feasible to speculate that the ZnO NPs may cross the BTB, inducing testicular toxicity, which is reinforced by in vivo studies that reported significant alterations in the testis after oral administration of ZnO NPs [14], even with lower doses, and by a recent study reporting an increase of Zn2+ accumulation in testis and epididymis [15]
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