title: Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress.
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 degrees 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.
authors.affiliation: Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, Yamagata, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Iuchi
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Noriko
authors.initials: N
authors.lastname: Kibe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shirasawa
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Junichi
authors.initials: J
authors.lastname: Fujii
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D016923:Cell Death / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro; D005434:Flow Cytometry; D005838:Genotype; D006358:Hot Temperature; D015151:Immunoblotting; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000235:genetics*; D054464:Peroxiredoxins / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D013090:Spermatocytes / Q000166:cytology* / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: D054464:Peroxiredoxins