Exploring novel function of Gpx5 antioxidant activity: Assisting epididymal cells secrete functional extracellular vesicles

J Cell Physiol. 2024 Jun;239(6):e31273. doi: 10.1002/jcp.31273. Epub 2024 Apr 26.

Abstract

Glutathione peroxisomal-5 (Gpx5) promotes the elimination of H2O2 or organic hydrogen peroxide, and plays an important role in the physiological process of resistance to oxidative stress (OS). To directly and better understand the protection of Gpx5 against OS in epididymal cells and sperm, we studied its mechanism of antioxidant protection from multiple aspects. To more directly investigate the role of Gpx5 in combating oxidative damage, we started with epididymal tissue morphology and Gpx5 expression profiles in combination with the mouse epididymal epithelial cell line PC1 (proximal caput 1) expressing recombinant Gpx5. The Gpx5 is highly expressed in adult male epididymal caput, and its protein signal can be detected in the sperm of the whole epididymis. Gpx5 has been shown to alleviate OS damage induced by 3-Nitropropionic Acid (3-NPA), including enhancing antioxidant activity, reducing mitochondrial damage, and suppressing cell apoptosis. Gpx5 reduces OS damage in PC1 and maintains the well-functioning extracellular vesicles (EVs) secreted by PC1, and the additional epididymal EVs play a role in the response of sperm to OS damage, including reducing plasma membrane oxidation and death, and increasing sperm motility and sperm-egg binding ability. Our study suggests that GPX5 plays an important role as an antioxidant in the antioxidant processes of epididymal cells and sperm, including plasma membrane oxidation, mitochondrial oxidation, apoptosis, sperm motility, and sperm-egg binding ability.

Keywords: Gpx5; extracellular vesicles; oxidative stress; sperm function.

MeSH terms

  • Aging
  • Animals
  • Antioxidants* / metabolism
  • Apoptosis / drug effects
  • Cell Line
  • Epididymis* / drug effects
  • Epididymis* / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Extracellular Vesicles* / drug effects
  • Extracellular Vesicles* / metabolism
  • Glutathione Peroxidase* / genetics
  • Glutathione Peroxidase* / metabolism
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Nitro Compounds
  • Oxidative Stress* / drug effects
  • Propionates / pharmacology
  • Sperm Motility / drug effects
  • Spermatozoa* / drug effects
  • Spermatozoa* / metabolism

Substances

  • 3-nitropropionic acid
  • Antioxidants
  • Glutathione Peroxidase
  • Nitro Compounds
  • Propionates