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

摘要

Purpose: Lanthanum oxide (Lasub2/subOsub3/sub) 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 Lasub2/subOsub3/sub particles in the testes. Materials and Methods: Fifty Kunming mice were randomly divided into five groups. Mice were treated with Lasub2/subOsub3/sub 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 Lasub2/subOsub3/sub 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 Lasub2/subOsub3/sub NPs or not had no difference; sperm parameters and histological assessment showed that Lasub2/subOsub3/sub 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 Lasub2/subOsub3/sub NPs were more severe than Lasub2/subOsub3/sub MPs in the testes. Furthermore, Lasub2/subOsub3/sub 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 Lasub2/subOsub3/sub NPs improved the spermatogenesis defects in mice. Lasub2/subOsub3/sub NPs inhibited Nrf-2/ARE signaling pathway that resulted in apoptosis in the mice testes.