Involvement of selenoprotein P and GPx4 gene expression in cadmium-induced testicular pathophysiology in rat

To investigate the effect of co-exposure to cadmium (Cd) and selenium (Se) on selenoprotein P (SelP) and phospholipid hydroperoxide glutathione peroxidase (GPx4) gene expression in testis and to evaluate their possible involvement in Cd-induced testicular pathophysiology, male rats received either tap water, Cd or Cd + Se in their drinking water for 5 weeks. Cd exposure caused a down-regulation of SelP and GPx4 gene expression and a significant decrease in plasma and testicular concentrations of Se. These changes were accompanied by decreased plasma testosterone level, sperm count and motility, GSH content, protein-bound sulfhydryl concentration (PSH), enzymatic activities of catalase (CAT) and glutathione peroxidase (GSH-Px) as well as by increased glutathione-S-transferase (GST) activity, lipid peroxidation (as malondialdehyde, MDA) and proteins carbonyls (PC). The decrease of testicular SelP and GPx4 gene expression under Cd influence was significantly restored in Cd + Se group. Co-treatment with Cd and Se also totally reversed the Cd-induced depletion of Se, decrease in plasma testosterone level and partially restored Cd-induced oxidative stress and decrease in sperm count and motility. Taken together, these data suggest that down-regulation of SelP and GPx4 gene expression induces plasma and testicular Se depletion leading, at least in part, to Cd-induced testicular pathophysiology.