Postnatal expression profiles of phospholipid hydroperoxide glutathioneperoxidase in spermatogenesis in mice
Postnatal expression profiles of phospholipid hydroperoxide glutathioneperoxidase in spermatogenesis in mice
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is known to be an antioxidant enzyme that may be implicated in spermatogenesis, but its functional significance in the development of testes remains poorly understood. To demonstrate the roles of PHGPx in spermatogenesis during postnatal development, expression profiles of PHGPx mRNA and protein in testes and epididymides obtained from mice 1 9 and 27 weeks after birth were spatiotemporally analyzed. In testes, PHGPx mRNA first appeared in 2-week-old mice, while its protein was first detected in late spermatocytes and round spermatids from 3-week-old mice and levels were greatly increased in elongated spermatids and immature spermatozoa of 5-week-old mice. These increased levels were maintained until 27 weeks as well as weak expression in Leydig cells. In the epididymides, PHGPx mRNA was weakly detected in all ages examined, while PHGPx protein first appeared at 4 weeks, greatly increased after 6 weeks, and was observed strongly in luminal sperm and weakly in surrounding tubular epithelium until 27 weeks. These findings indicate that PHGPx is essential for postnatal spermatogenic activity in mice.
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- 1. Imai H, Nakagawa Y. Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells. Free Radic Biol Med 2003; 34: 145169.
- 2. Imai H, Narashima K, Arai M, Sakamoto H, Chiba N, Nakagawa Y. Suppression of leukotriene formation in RBL-2H3 cells that overexpressed phospholipid hydroperoxide glutathione peroxidase. Biol Chem 1998; 273: 19901997.
- 3. Liang H, Van Remmen H, Frohlich V, Lechleiter J, Richardson A, Ran Q. Gpx4 protects mitochondrial ATP generation against oxidative damage. Biochem Biophys Res Commun 2007; 356: 893898.
- 4. Imai H, Sumi D, Hanamoto A, Arai M, Sugiyama A. Molecular cloning and functional expression of a cDNA for rat phospholipid hydroperoxide glutathione peroxidase: 3-untranslated region of the gene is necessary for functional expression. J Biochem 1995; 118: 10611067.
- 5. Nam SY, Fujisawa M, Kim JS, Kurohmaru M, Hayashi Y. Expression pattern of phospholipid hydroperoxide glutathione peroxidase messenger ribonucleic acid in mouse testis. Biol Reprod 1998; 58: 12721276.
- 6. Liang H, Yoo SE, Na R, Walter CA, Richardson A, Ran Q. Short form glutathione peroxidase 4 is the essential isoform required for survival and somatic mitochondrial functions. J Biol Chem 2009; 284: 3083630844.
- 7. Schneider M, Förster H, Boersma A, Seiler A, Wehnes H, Sinowatz F, Neumüller C, Deutsch MJ, Walch A, Hrabé de Angelis M et al. Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J 2009; 23: 32333242.
- 8. Foresta C, Flohé L, Garolla A, Roveri A, Ursini F, Maiorino M. Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol Reprod 2002; 67: 967971.
- 9. Flohé L. Selenium in mammalian spermiogenesis. Biol Chem 2007; 388: 987995.
- 10. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2ΔΔCT method. Methods 2001; 25: 402408.
- 11. Yon JM, Baek IJ, Lee SR, Kim MR, Lee BJ, Yun YW, Nam SY. Immunohistochemical identification and quantitative analysis of cytoplasmic Cu/Zn superoxide dismutase in mouse organogenesis. J Vet Sci 2008; 9: 233240.
- 12. Rugh R. The Mouse. 1st ed. New York, NY, USA: Oxford University Press; 1990.
- 13. Nayernia K, Diaconu M, Aumüller G, Wennemuth G, Schwandt I, Kleene K, Kuehn H, Engel W. Phospholipid hydroperoxide glutathione peroxidase: expression pattern during testicular development in mouse and evolutionary conservation in spermatozoa. Mol Reprod Dev 2004; 67: 458464.
- 14. Roveri A, Casasco A, Maiorino M, Dalan P, Calligaro A, Ursini F. Phospholipid hydroperoxide glutathione peroxidase of rat testis. Gonadotropin dependence and immunocytochemical identification. J Biol Chem 1992; 267: 61426146.
- 15. Rockett JC, Mapp FL, Garges JB, Luft JC, Mori C, Dix DJ. Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol Reprod 2001; 65: 229239.
- 16. Jung KY, Yon JM, Lin C, Jung AY, Lee JG, Baek IJ, Lee BJ, Yun YW, Nam SY. Phospholipid hydroperoxide glutathione peroxidase is involved in the maintenance of male fertility under cryptorchidism in mice. Reprod Toxicol 2015; 57: 7380.
- 17. Den Boer PJ, Poot M, Verkerk A, Jansen R, Mackenbach P, Grootegoed JA. Glutathione-dependent defence mechanisms in isolated round spermatids from the rat. Int J Androl 1990; 13: 2638.
- 18. Jervis KM, Robaire B. Dynamic changes in gene expression along the rat epididymis. Biol Reprod 2001; 65: 696703.
- 19. Chabory E, Damon C, Lenoir A, Kauselmann G, Kern H, Zevnik B, Garrel C, Saez F, Cadet R, Henry-Berger J et al. Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice. J Clin Invest 2009; 119: 20742085.