Spermatogenic Apoptosis and the Involvement of the Nrf2 Pathway in Male Mice Following Exposure to Nano Titanium Dioxide

Titanium dioxide nanoparticles (TiO₂ NPs) are largely manufactured and extensively applied for the treatment of environmental pollution. Studies have proved that exposure to TiO₂ NPs leads to toxicity of the reproductive system. However, very few studies have highlighted the involvement of nuclear factor erythroid-2 related factor 2 (Nrf2) under TiO₂ NPinduced spermatogenic apoptosis. Our findings suggested that TiO₂ NPs could cross the blood-testis barrier and were aggregated or deposed in spermatogenic cells, which resulted in spermatogenic apoptosis. Furthermore, exposure to TiO₂ NPs caused an overproduction of reactive oxygen species and the peroxidation of lipids, proteins, and DNA. Such exposure also caused significant decreases in the activities of SOD, GSH-PX, GST, and GSH content in the testis. Importantly, exposure to TiO₂ NPs resulted in an up-regulation of Keap1 expression and a down-regulation of Nrf2 and its target gene products, NQO1, HO-1, GCLC, PKC, and PI3K. The present study implies that TiO₂ NPs could lead to spermatogenic apoptosis, and Nrf2 is the initial factor that responded to such reproductive toxicity by regulating the expression of antioxidative proteins.