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.