Epididymis response partly compensates for spermatozoa oxidative defects in snGPx4 and GPx5 double mutant mice

• Published in: PloS one Vol. 7; no. 6; p. e38565
• Main Authors: Noblanc, Anaïs, Peltier, Manon, Damon-Soubeyrand, Christelle, Kerchkove, Nicolas, Chabory, Eléonore, Vernet, Patrick, Saez, Fabrice, Cadet, Rémi, Janny, Laurent, Pons-Rejraji, Hanae, Conrad, Marcus, Drevet, Joël R, Kocer, Ayhan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.06.2012; Public Library of Science (PLoS)
• Subjects: Abnormalities; Animals; Antioxidants; Biology; Cell culture; Chromosomes; Compaction; Deoxyribonucleic acid; DNA; DNA damage; DNA fragmentation; Enzymes; Epididymis; Epididymis - physiology; Fertility; Genetics; Glutathione; Glutathione peroxidase; Glutathione Peroxidase - genetics; Hydrogen peroxide; Laboratories; Life Sciences; Male; Males; Mammals; Medicine; Mice; Mice, Mutant Strains; Mice, Transgenic; Motility; Nuclei; Oxidation; Oxidative Stress; Peroxidase; Peroxiredoxin; Polymerase chain reaction; Pregnancy; Reproductive Biology; Reproductive technologies; Rodents; Salvage; Sperm; Spermatozoa; Spermatozoa - metabolism; Spermatozoa - physiology; Structural stability; Thioredoxin; Transferases; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038565

We report here that spermatozoa of mice lacking both the sperm nucleus glutathione peroxidase 4 (snGPx4) and the epididymal glutathione peroxidase 5 (GPx5) activities display sperm nucleus structural abnormalities including delayed and defective nuclear compaction, nuclear instability and DNA damage. We show that to counteract the GPx activity losses, the epididymis of the double KO animals mounted an antioxydant response resulting in a strong increase in the global H(2)O(2)-scavenger activity especially in the cauda epididymis. Quantitative RT-PCR data show that together with the up-regulation of epididymal scavengers (of the thioredoxin/peroxiredoxin system as well as glutathione-S-transferases) the epididymis of double mutant animals increased the expression of several disulfide isomerases in an attempt to recover normal disulfide-bridging activity. Despite these compensatory mechanisms cauda-stored spermatozoa of double mutant animals show high levels of DNA oxidation, increased fragmentation and greater susceptibility to nuclear decondensation. Nevertheless, the enzymatic epididymal salvage response is sufficient to maintain full fertility of double KO males whatever their age, crossed with young WT female mice.