In Vitro Cytotoxicity Effects of Zinc Oxide Nanoparticles on Spermatogonia Cells

authors	Pinho, AR; Martins, F; Costa, MEV; Senos, AMR; Silva, OABDE; Pereira, MD; Rebelo, S
nationality	International
journal	CELLS
author keywords	spermatogonia; ZnO nanoparticles; cytotoxicity; cell death; DNA damage; reactive oxygen species; cytoskeleton; nucleoskeleton
keywords	NUCLEAR-ENVELOPE RUPTURE; ZNO NANOPARTICLES; PROTEIN; ACTIN; SUN1; TOXICITY; TUBULIN; SPERMATOGENESIS; MAINTENANCE; HOMEOSTASIS
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.
publisher	MDPI
isbn	2073-4409
year published	2020
volume	9
issue	5
digital object identifier (doi)	10.3390/cells9051081
web of science category	Cell Biology
subject category	Cell Biology
unique article identifier	WOS:000539340200015