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 Prx4flox/+ 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.
Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress
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Yoshihito Iuchi, Futoshi Okada, Satoshi Tsunoda, Noriko Kibe, Nobuyuki Shirasawa, Masahito Ikawa, Masaru Okabe, Yoshitaka Ikeda, Junichi Fujii; Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress. Biochem J 1 April 2009; 419 (1): 149–158. doi: https://doi.org/10.1042/BJ20081526
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