<p>La<sub>2</sub>O<sub>3</sub> Nanoparticles Induce Reproductive Toxicity Mediated by the Nrf-2/ARE Signaling Pathway in Kunming Mice</p>
Yuan Lu, Qingzhao Li, Disi Bai, Xueliang Shang, Fen Hu, Zhenfei Chen, Tianyang An, Yajing Chen, Xiujun Zhang
Abstract
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. Keywords: La 2 O 3 nanoparticles, reproductive toxicity, inflammation, Nrf-2/ARE signaling pathway, apoptosis