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.
keywords
NUCLEAR-ENVELOPE RUPTURE; ZNO NANOPARTICLES; PROTEIN; ACTIN; SUN1; TOXICITY; TUBULIN; SPERMATOGENESIS; MAINTENANCE; HOMEOSTASIS
subject category
Cell Biology
authors
Pinho, AR; Martins, F; Costa, MEV; Senos, AMR; Silva, OABDE; Pereira, MD; Rebelo, S
our authors
Ana Maria de Oliveira e Rocha Senos
Associate Professor
Ana Rita Arede Pinho
PhD Student
Maria de Lourdes Gomes Pereira
Associate Professor with Aggregation
Maria Elisabete Jorge Vieira Costa
Assistant ProfessorGroups
G2 - Photonic, Electronic and Magnetic Materials
G5 - Biomimetic, Biological and Living Materials
acknowledgements
The present research was supported by the Instituto de Biomedicine-(iBiMED)(UID/BIM/04501/2020 and POCI-01-0145-FEDER-007628); and the Fundacao para a Ciencia e Tecnologia (FCT) of the Ministerio da Educacao e Ciencia, the COMPETE program, QREN, and the EU (Fundo Europeu de Desenvolvimento Regional). Authors acknowledge support from the project 'Wisdom-Impact of wide-spread proteome aggregation through aging in mammals and implications for the development of age-related diseases' (PTDC/BTM-TEC/29843/2017) and the Integrated Programme of SR&TD pAGE-Protein aggregation Across the Lifespan (reference CENTRO-01-0145-FEDER-000003), co-funded by Centro 2020 program, Portugal 2020, European Union, through the European Regional Development Fund. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC; and, when appropriate, was co-financed by FEDER under the PT2020 Partnership Agreement.