La₂O₃ Nanoparticles Induce Reproductive Toxicity Mediated by the Nrf-2/ARE Signaling Pathway in Kunming Mice

Lanthanum oxide (La₂O₃) 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 La₂O₃ particles in the testes.

Fifty Kunming mice were randomly divided into five groups. Mice were treated with La₂O₃ 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 La₂O₃ NPs. Sperm parameters, testicular histopathology, TEM assessment, hormone assay and nuclear factor erythroid 2-related factor 2 (Nrf-2) pathway were performed and evaluated.

The body weight of mice treated with La₂O₃ NPs or not had no difference; sperm parameters and histological assessment showed that La₂O₃ 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 La₂O₃ NPs were more severe than La₂O₃ MPs in the testes. Furthermore, La₂O₃ 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.

The results of this study demonstrated that La₂O₃ NPs improved the spermatogenesis defects in mice. La₂O₃ NPs inhibited Nrf-2/ARE signaling pathway that resulted in apoptosis in the mice testes.