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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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snGPx4;GPx5 deficiency leads to a strong epididymis anti-oxidant response.A: Histograms show global H2O2-scavenging activity using H2O2 as a substrate in caput or cauda epididymis tissue extracts from WT or DKO animals aged 4 months. To evaluate the extent of the epididymis anti-oxidant response global H2O2-scavenging activity in liver extracts of the same animals are shown on the left. (Mean +/− SEM; n = 5; **: p≤0.01 compared to WT) B: Malondialdehyde (MDA) measurements on caput and cauda epididymal tissues as well as on cauda-collected spermatozoa from WT and DKO animals aged 4 months. (Mean +/− SEM; n = 3; *: p≤0.05 compared to WT).
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pone-0038565-g006: snGPx4;GPx5 deficiency leads to a strong epididymis anti-oxidant response.A: Histograms show global H2O2-scavenging activity using H2O2 as a substrate in caput or cauda epididymis tissue extracts from WT or DKO animals aged 4 months. To evaluate the extent of the epididymis anti-oxidant response global H2O2-scavenging activity in liver extracts of the same animals are shown on the left. (Mean +/− SEM; n = 5; **: p≤0.01 compared to WT) B: Malondialdehyde (MDA) measurements on caput and cauda epididymal tissues as well as on cauda-collected spermatozoa from WT and DKO animals aged 4 months. (Mean +/− SEM; n = 3; *: p≤0.05 compared to WT).

Mentions: Figure 6A shows that in the double mutant animals, global H2O2-scavenging activity was up-regulated especially in the cauda compartment. The global H2O2-scavenging activity recorded in the double mutant cauda territory exceeded by far that recorded in the same compartment in WT animals. As a physiological indicator, Figure 6A, also shows that the global H2O2-scavenging activity recorded in the epididymis of double mutant animals was quite comparable to that found in liver, a tissue well-known for its high ROS-recycling metabolism. It is also important to note that, in the double mutant animals, the epididymis but not the liver was engaged in this global antioxidant response. As a result, the content in malonyldialdehyde (MDA), an end-point marker of lipid peroxidation, was significantly lower in spermatozoa of double mutant animals when compared to WT (Figure 6B). In caput and cauda tissue extracts, the MDA content was similar when WT samples were compared to KO samples. This suggests that the surnumerary protection against lipid peroxidation engaged by the cauda epididymis was of a secreted nature or already present in the vicinity or on the sperm cell itself.


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)

snGPx4;GPx5 deficiency leads to a strong epididymis anti-oxidant response.A: Histograms show global H2O2-scavenging activity using H2O2 as a substrate in caput or cauda epididymis tissue extracts from WT or DKO animals aged 4 months. To evaluate the extent of the epididymis anti-oxidant response global H2O2-scavenging activity in liver extracts of the same animals are shown on the left. (Mean +/− SEM; n = 5; **: p≤0.01 compared to WT) B: Malondialdehyde (MDA) measurements on caput and cauda epididymal tissues as well as on cauda-collected spermatozoa from WT and DKO animals aged 4 months. (Mean +/− SEM; n = 3; *: p≤0.05 compared to WT).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038565-g006: snGPx4;GPx5 deficiency leads to a strong epididymis anti-oxidant response.A: Histograms show global H2O2-scavenging activity using H2O2 as a substrate in caput or cauda epididymis tissue extracts from WT or DKO animals aged 4 months. To evaluate the extent of the epididymis anti-oxidant response global H2O2-scavenging activity in liver extracts of the same animals are shown on the left. (Mean +/− SEM; n = 5; **: p≤0.01 compared to WT) B: Malondialdehyde (MDA) measurements on caput and cauda epididymal tissues as well as on cauda-collected spermatozoa from WT and DKO animals aged 4 months. (Mean +/− SEM; n = 3; *: p≤0.05 compared to WT).
Mentions: Figure 6A shows that in the double mutant animals, global H2O2-scavenging activity was up-regulated especially in the cauda compartment. The global H2O2-scavenging activity recorded in the double mutant cauda territory exceeded by far that recorded in the same compartment in WT animals. As a physiological indicator, Figure 6A, also shows that the global H2O2-scavenging activity recorded in the epididymis of double mutant animals was quite comparable to that found in liver, a tissue well-known for its high ROS-recycling metabolism. It is also important to note that, in the double mutant animals, the epididymis but not the liver was engaged in this global antioxidant response. As a result, the content in malonyldialdehyde (MDA), an end-point marker of lipid peroxidation, was significantly lower in spermatozoa of double mutant animals when compared to WT (Figure 6B). In caput and cauda tissue extracts, the MDA content was similar when WT samples were compared to KO samples. This suggests that the surnumerary protection against lipid peroxidation engaged by the cauda epididymis was of a secreted nature or already present in the vicinity or on the sperm cell itself.

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