TiO2 nanoparticles-induced apoptosis of primary cultured Sertoli cells of mice.

Titanium dioxide nanoparticles (TiO₂ NPs), as largest production and use of nanomaterials, have been demonstrated to have a potential toxicity on reproductive system. However, the mechanism underlying male reproductive toxicity of TiO₂ NPs remains limited. Thus, our study was designed to examine the cellular viability, apoptosis, oxidative stress, antioxidant capacity, and expression of apoptotic cytokines in primary cultured Sertoli cells isolated from mice under TiO₂ NPs exposure. Results showed that TiO₂ NPs exposure from 5 to 30 μg/mL resulted in reduction of cell viability, lactate dehydrogenase release, and induction of apoptosis or death on Sertoli cells. TiO₂ NPs could migrate to Sertoli cells, which induced mitochondria-mediated or endoplasmic-reticulum-mediated apoptotic changes including elevation in reactive oxygen species (ROS) generation and reductions in superoxide dismutase, catalase, and glutathione peroxidase activities, decreases in mitochondrial membrane potential (DWm), and releases of cytochrome c into the cytosol. In addition, upregulation of cytochrome c, Bax, caspase-3, glucose-regulated protein 78, and C/ EBP homologous protein and caspase-12 protein expression, and downregulation of bcl-2 protein expression in primary cultured Sertoli cells induced by TiO₂ NPs treatment. All of the results suggested that ROS generation may play a critical role in the initiation of TiO₂ NPs-induced apoptosis by mediation of the disruption of Δψm, the cytochrome c release, and further the activation of caspase cascade and unfolded protein response signaling pathway. [ABSTRACT FROM AUTHOR]