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

Chem Biol Interact. 2010 Oct 6;188(1):94-101. doi: 10.1016/j.cbi.2010.07.012. Epub 2010 Jul 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cadmium / toxicity*
  • DNA Primers
  • Gene Expression Regulation / drug effects*
  • Glutathione Peroxidase / genetics*
  • Lipid Peroxidation
  • Male
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Polymerase Chain Reaction
  • Rats
  • Selenoprotein P / genetics*
  • Spermatozoa / physiology
  • Testis / drug effects*
  • Testis / physiopathology
  • Testosterone / blood

Substances

  • DNA Primers
  • Selenoprotein P
  • Cadmium
  • Testosterone
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Glutathione Peroxidase
  • glutathione peroxidase 4, rat