La(2)O(3) Nanoparticles Induce Reproductive Toxicity Mediated by the Nrf-2/ARE Signaling Pathway in Kunming Mice

PURPOSE: Lanthanum oxide (La(2)O(3)) nanoparticles (NPs) have been widely used in catalytic and photoelectric applications, but the reproductive toxicity is still unclear. This study evaluated the reproductive toxicity of two different-sized La(2)O(3) particles in the testes. MATERIALS AND METHODS: Fifty Kunming mice were randomly divided into five groups. Mice were treated with La(2)O(3) NPs by repeated intragastric administration for 90 days (control, nano-sized with 5, 10, 50 mg/kg BW and micro-sized with 50 mg/kg BW). Mice in the control group were treated with de-ionised water without La(2)O(3) NPs. Sperm parameters, testicular histopathology, TEM assessment, hormone assay and nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway were performed and evaluated. RESULTS: The body weight of mice treated with La(2)O(3) NPs or not had no difference; sperm parameters and histological assessment showed that La(2)O(3) NPs could induce reproductive toxicity in the testicle. Serum testosterone and gonadotropin-releasing hormone (GnRH) in the NH (nano-sized with 50 mg/kg BW) group were markedly decreased relative to control group, and an increase of luteinizing hormone (LH) in NH group was detected . Additionally, transmission electron microscopy revealed that the ultrastructural abnormalities induced by La(2)O(3) NPs were more severe than La(2)O(3) MPs in the testes. Furthermore, La(2)O(3) NPs treatment inhibited the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm into the nucleus as well as the expression of downstream genes NAD(P)H quinone oxidoreductase1 (NQO1), hemeoxygenase 1 (HO-1) and (glutathione peroxidase) GSH-Px, thus abrogating Nrf-2-mediated defense mechanisms against oxidative stress. CONCLUSIONS: The results of this study demonstrated that La(2)O(3) NPs improved the spermatogenesis defects in mice. La(2)O(3) NPs inhibited Nrf-2/ARE signaling pathway that resulted in apoptosis in the mice testes.