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

Noblanc A, Peltier M, Damon-Soubeyrand C, Kerchkove N, Chabory E, Vernet P, Saez F, Cadet R, Janny L, Pons-Rejraji H, Conrad M, Drevet JR, Kocer A - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Genetics Reproduction & Development laboratory, CNRS UMR 6293 - INSERM U1103 - Clermont Université, Aubière, France.

ABSTRACT
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.

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Evaluation of sperm DNA condensation using toluidine blue staining.A: The photograph shows a typical result of toluidine blue staining on a decondensed caput sperm DNA (arrowhead) compared to a condensed caput sperm DNA (arrow). Scale bar = 5 µm. B and C: Histograms plotting the proportion of decondensed sperm nucleus found in WT, sngpx4−/− and DKO caput sperm population (B) and cauda sperm population (C) in animals aged 4 or 8 months. (Mean +/− SEM; n = 5; ***: p≤0.001 compared to WT).
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pone-0038565-g002: Evaluation of sperm DNA condensation using toluidine blue staining.A: The photograph shows a typical result of toluidine blue staining on a decondensed caput sperm DNA (arrowhead) compared to a condensed caput sperm DNA (arrow). Scale bar = 5 µm. B and C: Histograms plotting the proportion of decondensed sperm nucleus found in WT, sngpx4−/− and DKO caput sperm population (B) and cauda sperm population (C) in animals aged 4 or 8 months. (Mean +/− SEM; n = 5; ***: p≤0.001 compared to WT).

Mentions: As shown by toluidine blue staining in caput and cauda sperm of the double KO animals at 4 months and 8 months of age, a large proportion (up to 80%) of the double mutant caput sperm population showed defective nuclear condensation (Figure 2A and 2B). However, sperm DNA compaction resumed an apparently normal level in cauda-collected spermatozoa of the double mutants (Fig. 2C).


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

Noblanc A, Peltier M, Damon-Soubeyrand C, Kerchkove N, Chabory E, Vernet P, Saez F, Cadet R, Janny L, Pons-Rejraji H, Conrad M, Drevet JR, Kocer A - PLoS ONE (2012)

Evaluation of sperm DNA condensation using toluidine blue staining.A: The photograph shows a typical result of toluidine blue staining on a decondensed caput sperm DNA (arrowhead) compared to a condensed caput sperm DNA (arrow). Scale bar = 5 µm. B and C: Histograms plotting the proportion of decondensed sperm nucleus found in WT, sngpx4−/− and DKO caput sperm population (B) and cauda sperm population (C) in animals aged 4 or 8 months. (Mean +/− SEM; n = 5; ***: p≤0.001 compared to WT).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375294&req=5

pone-0038565-g002: Evaluation of sperm DNA condensation using toluidine blue staining.A: The photograph shows a typical result of toluidine blue staining on a decondensed caput sperm DNA (arrowhead) compared to a condensed caput sperm DNA (arrow). Scale bar = 5 µm. B and C: Histograms plotting the proportion of decondensed sperm nucleus found in WT, sngpx4−/− and DKO caput sperm population (B) and cauda sperm population (C) in animals aged 4 or 8 months. (Mean +/− SEM; n = 5; ***: p≤0.001 compared to WT).
Mentions: As shown by toluidine blue staining in caput and cauda sperm of the double KO animals at 4 months and 8 months of age, a large proportion (up to 80%) of the double mutant caput sperm population showed defective nuclear condensation (Figure 2A and 2B). However, sperm DNA compaction resumed an apparently normal level in cauda-collected spermatozoa of the double mutants (Fig. 2C).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Genetics Reproduction & Development laboratory, CNRS UMR 6293 - INSERM U1103 - Clermont Université, Aubière, France.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus