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Peroxiredoxin 4knockout results in elevated spermatogenic cell death via oxidative stress
- Source :
- Biochemical Journal. 419:149-158
- Publication Year :
- 2009
- Publisher :
- Portland Press Ltd., 2009.
-
Abstract
- Prx (peroxiredoxin) is a multifunctional redox protein with thioredoxin-dependent peroxidase activity. Prx4 is present as a secretory protein in most tissues, whereas in sexually mature testes it is anchored in the ER (endoplasmic reticulum) membrane of spermatogenic cells via an uncleaved N-terminal hydrophobic peptide. We generated a Prx4 knockout mouse to investigate the function of Prx4 in vivo . Prx4 −/ y mice lacking Prx4 expression in all cells were obtained by mating Prx4 flox /+ female mice with Cre-transgenic male mice that ubiquitously expressed Cre recombinase. The resulting Prx4 −/ y male mice were fertile, and most organs were nearly normal in size, except for testicular atrophy. The number of deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive spermatogenic cells was higher in Prx4 −/ y mice than in Prx4 +/ y mice and increased remarkably in response to warming the lower abdomen at 43 °C for 15 min. Cells reactive to antibodies against 4-hydroxynonenal and 8-hydroxyguanine were high in the Prx4 −/ y mice and concomitant with elevated oxidation of lipid and protein thiols. The cauda epididymis of Prx4 −/ y mice contained round spermatocytes, which were not found in Prx4 +/ y mice, and displayed oligozoospermia. However, mature spermatozoa from the epididymis of Prx4 −/ y mice exhibited normal fertilization In vitro . Taken together, these results indicate that spermatogenic cells lacking Prx4 are more susceptible to cell death via oxidative damage than their wild-type counterparts. Our results suggest that the presence of Prx4, most likely the membrane-bound form, is important for spermatogenesis, but not an absolute requisite.
- Subjects :
- Male
Programmed cell death
Hot Temperature
Genotype
Immunoblotting
Fertilization in Vitro
Biology
Polymerase Chain Reaction
Biochemistry
Mice
Microscopy, Electron, Transmission
Spermatocytes
Testis
medicine
Animals
Molecular Biology
Mice, Knockout
Spermatogenic Cell
Cell Death
Endoplasmic reticulum
Peroxiredoxins
Cell Biology
Blotting, Northern
Flow Cytometry
Epididymis
Immunohistochemistry
Molecular biology
Mice, Inbred C57BL
Oxidative Stress
Secretory protein
medicine.anatomical_structure
Knockout mouse
Female
Lipid Peroxidation
Peroxiredoxin
Spermatogenesis
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 419
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....afdb0e54e480afcdea0d93bb2535c7c2