Epididymis response partly compensates for spermatozoa oxidative defects in snGPx4 and GPx5 double mutant mice.
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.
Genetics Reproduction & Development laboratory, CNRS UMR 6293 - INSERM U1103 - Clermont Université, Aubière, France.
Anaïs
A
Noblanc
Manon
M
Peltier
Christelle
C
Damon-Soubeyrand
Nicolas
N
Kerchkove
Eléonore
E
Chabory
Patrick
P
Vernet
Fabrice
F
Saez
Rémi
R
Cadet
Laurent
L
Janny
Hanae
H
Pons-Rejraji
Marcus
M
Conrad
Joël R
JR
Drevet
Ayhan
A
Kocer
D000818:Animals; D004822:Epididymis / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D018384:Oxidative Stress; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology*
D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C080439:selenium-independent glutathione peroxidase