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Heat and Oxidative Stress in the Germ Line

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Studies on Men's Health and Fertility

Abstract

Spermatogenesis is highly dependent on scrotal temperature. In the ­testis, germ cells but not somatic cells are vulnerable to heat stress. In response to heat stress, germ cells undergo apoptosis, autophagy, necrosis, and cell cycle arrest; these behaviors are different in each testicular component. Heat induces oxidative stress in the testicles in a variety of ways, mainly by lipid peroxidation of the cellular membrane and mitochondria-derived reactive oxygen species (ROS), and heat-induced oxidative stress is involved in all of these cellular behaviors. Heat-shock factor 1 (HSF1) protects the cells by regulating the expression of heat-shock proteins (HSPs), promoting cell survival. Paradoxically, HSF1 promotes apoptosis of germ cells by heat stress, indicating that injured germ cells actively undergo apoptosis to maintain the quality of gametes. The pattern of heat stress (degree, duration, and interval of the elevated temperature) in humans (e.g., cryptorchidism, varicocele, and environmental heat exposure) is completely different compared to in vitro and in vivo animal experiments.

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References

  1. Setchell BP. The Parkes Lecture. Heat and the testis. J Reprod Fertil. 1998;114:179–94.

    Article  PubMed  CAS  Google Scholar 

  2. Ivell R. Lifestyle impact and the biology of the human scrotum. Reprod Biol Endocrinol. 2007;5:e15.

    Article  Google Scholar 

  3. Yaeram J, Setchell BP, Maddocks S. Effect of heat stress on the fertility of male mice in vivo and in vitro. Reprod Fertil Dev. 2006;18:647–53.

    Article  PubMed  CAS  Google Scholar 

  4. Mieusset R, Bujan L, Mondinat C, et al. Association of scrotal hyperthermia with impaired spermatogenesis in infertile men. Fertil Steril. 1987;48:1006–11.

    PubMed  CAS  Google Scholar 

  5. Jannes P, Spiessens C, van der Auwera I, et al. Male subfertility induced by acute scrotal heating affects embryo quality in normal female mice. Hum Reprod. 1998;13:372–5.

    Article  PubMed  CAS  Google Scholar 

  6. Rockett JC, Mapp FL, Garges JB, et al. Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol Reprod. 2001;65:229–39.

    Article  PubMed  CAS  Google Scholar 

  7. Zhu BK, Setchell BP. Effects of paternal heat stress on the in vivo development of preimplantation embryos in the mouse. Reprod Nutr Dev. 2004;44:617–29.

    Article  PubMed  Google Scholar 

  8. Turner TT, Lysiak JJ. Oxidative stress: a common factor in testicular dysfunction. J Androl. 2008;29:488–98.

    Article  PubMed  CAS  Google Scholar 

  9. Yu BP. Cellular defense against damage from reactive oxygen species. Physiol Rev. 1994;74:139–62.

    PubMed  CAS  Google Scholar 

  10. Alvarez JG, Storey BT. Spontaneous lipid peroxidation in rabbit and mouse epididymal spermatozoa: dependence of rate on temperature and oxygen concentration. Biol Reprod. 1985;32:342–51.

    Article  PubMed  CAS  Google Scholar 

  11. Ahutopa M, Huhtaniemi I. Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally cryptorchid rat testis. Biol Reprod. 1992;46:1114–8.

    Article  Google Scholar 

  12. Peltola V, Huhtaniemi I, Ahotupa M. Abdominal position of the rat testis is associated with high level of lipid peroxidation. Biol Reprod. 1995;53:1146–50.

    Article  PubMed  CAS  Google Scholar 

  13. Ikeda M, Kodama H, Fukuda J, et al. Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress. Biol Reprod. 1999;61:393–9.

    Article  PubMed  CAS  Google Scholar 

  14. Cividalli A, Cruciani G, Livdi E, et al. Hyperthermia enhances the response of paclitaxel and radiation in a mouse adenocarcinoma. Int J Radiat Oncol Biol Phys. 1999;44:407–12.

    Article  PubMed  CAS  Google Scholar 

  15. Shiraishi K, Naito K, Yoshida K. Nitric oxide promotes germ cell necrosis in the delayed phase after experimental testicular torsion of rat. Biol Reprod. 2001;65:514–21.

    Article  PubMed  CAS  Google Scholar 

  16. Iuchi Y, Kaneko T, Matsuki S, et al. Carbonyl stress and detoxification ability in the male genital tract and testis of rats. Histochem Cell Biol. 2004;121:123–30.

    Article  PubMed  CAS  Google Scholar 

  17. Bonfoco E, Krainc D, Ankarcrona M, et al. Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-d-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA. 1995;92:7162–6.

    Article  PubMed  CAS  Google Scholar 

  18. Guo J, Jia Y, Tao S-X, et al. Expression of nitric oxide synthase during germ cell apoptosis in testis of Cynomolgus monkey after testosterone and heat treatment. J Androl. 2009;30:190–9.

    Article  PubMed  CAS  Google Scholar 

  19. Shiratsuchi A, Umeda M, Ohba Y, et al. Recognition of phosphatidylserine on the surface of apoptotic spermatogenic cells and subsequent phagocytosis by Sertoli cells of the rat. J Biol Chem. 1997;272:2354–8.

    Article  PubMed  CAS  Google Scholar 

  20. Lue Y, Wang C, Liu YX, et al. Transient testicular warming enhances the suppressive effect of testosterone on spermatogenesis in adult cynomolgus monkeys (Macaca fascicularis). J Clin Endocrinol Metab. 2006;91:539–45.

    Article  PubMed  CAS  Google Scholar 

  21. Shiraishi K, Naito K. Nitric oxide produced in the testis is involved in dilatation of the internal spermatic vein that compromises spermatogenesis in infertile men with varicocele. BJU Int. 2007;99:1086–90.

    Article  PubMed  CAS  Google Scholar 

  22. Ishikawa T, Kondo Y, Goda K, et al. Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism. J Androl. 2005;26:281–8.

    PubMed  CAS  Google Scholar 

  23. Mieusset R, Bujan L. Testicular heating and its possible contribution to male infertility: a review. Int J Androl. 1995;18:169–84.

    Article  PubMed  CAS  Google Scholar 

  24. Jung A, Eberl M, Schill WB. Improvement of semen quality by nocturnal scrotal cooling and moderate behavioural change to reduce genital heat stress in men with oligoasthenoteratozoospermia. Reproduction. 2001;121:433–8.

    Article  Google Scholar 

  25. Lin P, Quamo S, Ho K, et al. Hyperthermia enhances the cytotoxic effects of reactive oxygen species to Chinese hamster and bovine endothelial cells in vitro. Radiat Res. 1991;126:43–51.

    Article  PubMed  CAS  Google Scholar 

  26. Flanagan SW, Moseley PL, Buettner GR. Increased flux of free radicals in cells subjected to hyperthermia: detection by electron paramagnetic resonance spin trapping. FEBS Lett. 1998;431:285–6.

    Article  PubMed  CAS  Google Scholar 

  27. Loven DP. A role for reduced oxygen species in heat-induced cell killing and the induction of thermotolerance. Med Hypotheses. 1988;26:39–50.

    Article  PubMed  CAS  Google Scholar 

  28. Lord-Fontaine S, Averil-Bates DA. Enhancement of cytotoxicity of hydrogen peroxide by hyperthermia in Chinese hamster ovary cells: role of antioxidant defenses. Arch Biochem Biophys. 1999;363:283–95.

    Article  PubMed  CAS  Google Scholar 

  29. Lindegaard JC. Thermosensitization induced by step-down heating. A review on heat-induced sensitization to hyperthermia alone or hyperthermia combined with radiation. Int J Hyperthermia. 1992;8:561–86.

    Article  PubMed  CAS  Google Scholar 

  30. Dewey WC. Arrhenius relationships from the molecule and cell to the clinic. Int J Hyperthermia. 2009;25:3–20.

    Article  PubMed  CAS  Google Scholar 

  31. Sinha Hikim AP, Lue Y, Yamamoto CM, et al. Key apoptotic pathways for heat-induced programmed cell death in the testis. Endocrinology. 2003;144:3167–75.

    Article  CAS  Google Scholar 

  32. Sinha-Hikim AP, Lue Y, Diaz-Romero M, et al. Deciphering the pathways of germ cell apoptosis in the testis. J Steroid Biochem Mol Biol. 2003;85:175–82.

    Article  PubMed  CAS  Google Scholar 

  33. Vera Y, Rodriguez S, Castanares M, et al. Functional role of caspases in heat-induced testicular germ cell apoptosis. Biol Reprod. 2005;72:516–22.

    Article  PubMed  CAS  Google Scholar 

  34. Choi JY, Jo MW, Lee EY, et al. The role of autophagy in follicular development and atresia in rat granulosa cells. Fertil Steril. 2010;93:2532–7.

    Article  PubMed  Google Scholar 

  35. Tsukamoto S, Kuma A, Murakami M, et al. Autophagy is essential for preimplantation development of mouse embryos. Science. 2008;321:117–20.

    Article  PubMed  CAS  Google Scholar 

  36. Chowdhury A, Steinberger E. A quantitative study of the effect of heat on germinal epithelium of rat testes. Am J Anat. 1964;115:509–24.

    Article  PubMed  CAS  Google Scholar 

  37. Pérez-Crespo M, Pintado B, Gutiérrez-Adán A. Scrotal heat stress effects on sperm viability, sperm DNA integrity, and the offspring sex ratio in mice. Mol Reprod Dev. 2008;75:40–7.

    Article  PubMed  CAS  Google Scholar 

  38. Paul C, Murray AA, Spears N, et al. A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction. 2008;136:73–84.

    Article  PubMed  CAS  Google Scholar 

  39. Paul C, Teng S, Saunders PT. A single, mild, transient scrotal heat stress causes hypoxia and oxidative stress in mouse testes, which induces germ cell death. Biol Reprod. 2009;80:913–9.

    Article  PubMed  CAS  Google Scholar 

  40. Yin Y, Hawkins KL, DeWolf WC, et al. Heat stress causes testicular germ cell apoptosis in adult mice. J Androl. 1997;18:159–65.

    PubMed  CAS  Google Scholar 

  41. Yamamoto CM, Sinha Hikim AP, Huynh PN, et al. Redistribution of bax is an early step in an apoptotic pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia. Biol Reprod. 2000;63:1683–90.

    Article  PubMed  CAS  Google Scholar 

  42. Cataldo L, Mastrangelo MA, Kleene KC. Differential effects of heat shock on translation of normal mRNAs in primary spermatocytes, elongated spermatids, and Sertoli cells in seminiferous tubule culture. Exp Cell Res. 1997;231:206–13.

    Article  PubMed  CAS  Google Scholar 

  43. Perez-Crespo M, Pintado B, Gutierrez-Adan A. Scrotal heat stress effects on sperm viability, sperm DNA integrity, and the offspring sex ratio in mice. Mol Reprod Dev. 2007;75:40–7.

    Article  CAS  Google Scholar 

  44. Hadziselimovic F, Herzog B. The importance of both an early orchidopexy and germ cell maturation for fertility. Lancet. 2001;358:1156–7.

    Article  PubMed  CAS  Google Scholar 

  45. de Rooij DG, Okabe M, Nishimune Y. Arrest of spermatogonial differentiation in jsd/jsd, Sl17H/Sl17H, and cryptorchid mice. Biol Reprod. 1999;61:842–7.

    Article  PubMed  Google Scholar 

  46. Diemer T, Allen JA, Hales KH, et al. Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology. 2003;144:2882–91.

    Article  PubMed  CAS  Google Scholar 

  47. Ren L, Medan MS, Ozu M, et al. Effects of experimental cryptorchidism on sperm motility and testicular endocrinology in adult male rats. J Reprod Dev. 2006;52:219–28.

    Article  PubMed  CAS  Google Scholar 

  48. Hendricks KEM, Martins L, Hansen PJ. Consequences for the bovine embryo of being derived from a spermatozoan subjected to post-ejaculatory aging and heat shock: development to the blastocyst stage and sex ratio. J Reprod Dev. 2009;55:69–74.

    Article  PubMed  CAS  Google Scholar 

  49. Zhu BK, Setchell BP. Effects of paternal heat stress on the in vivo development of preimplantation embryos in the mouse. Reprod Nutr Dev. 2004;44:617–29.

    Article  PubMed  Google Scholar 

  50. Nakai A, Suzuki M, Tanabe M. Arrest of spermatogenesis in mice expressing an active heat shock transcription factor 1. EMBO J. 2000;19:1545–54.

    Article  PubMed  CAS  Google Scholar 

  51. Ohta H, Aizawa S, Nishimune Y. Functional analysis of the p53 gene in apoptosis induced by heat stress or loss of stem cell factor signaling in mouse male germ cells. Biol Reprod. 2003;68:2249–54.

    Article  PubMed  CAS  Google Scholar 

  52. Izu H, Inoue S, Fujimoto M, et al. Heat shock transcription factor 1 is involved in quality control mechanism in male germ cells. Biol Reprod. 2004;70:18–24.

    Article  PubMed  CAS  Google Scholar 

  53. Ku JH, Shim HB, Kim SW, et al. The role of apoptosis in the pathogenesis of varicocele. BJU Int. 2005;96:1092–6.

    Article  PubMed  CAS  Google Scholar 

  54. Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol. 2010;28:359–64.

    Article  PubMed  CAS  Google Scholar 

  55. Lue YH, Sinha Hikim AP, Swerdloff RS, et al. Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology. 1999;140:1709–17.

    Article  PubMed  CAS  Google Scholar 

  56. Sakahira H, Enari M, Nagata S. Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature. 1998;391:96–9.

    Article  PubMed  CAS  Google Scholar 

  57. Shaha C, Tripathi R, Mishra DP. Male germ cell apoptosis: regulation and biology. Philos Trans R Soc Lond B Biol Sci. 2010;365:1501–15.

    Article  PubMed  CAS  Google Scholar 

  58. Lee J, Richburg JH, Shipp EB, et al. The Fas system, a regulator of testicular germ cell apoptosis, is differentially up-regulated in Sertoli cell versus germ cell injury of the testis. Endocrinology. 1999;140:852–8.

    Article  PubMed  CAS  Google Scholar 

  59. Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999;341:233–49.

    Article  PubMed  CAS  Google Scholar 

  60. Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev. 1979;59:527–605.

    PubMed  CAS  Google Scholar 

  61. Nagata S, Golstein P. The Fas death factor. Science. 1995;267:1449–56.

    Article  PubMed  CAS  Google Scholar 

  62. Hengartner MO. The biochemistry of apoptosis. Nature. 2000;407:770–6.

    Article  PubMed  CAS  Google Scholar 

  63. Cory S, Adams JM. The Bcl-2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647–56.

    Article  PubMed  CAS  Google Scholar 

  64. Maheshwari A, Misro MM, Aggarwal A, et al. Pathways involved in testicular germ cell apoptosis induced by H2O2 in vitro. FEBS J. 2009;276:870–81.

    Article  PubMed  CAS  Google Scholar 

  65. Jia Y, Castellamos J, Wang C, et al. Migotgen-activated protein kinase signaling in male germ cell apoptosis in the rat. Biol Reprod. 2009;80:771–80.

    Article  PubMed  CAS  Google Scholar 

  66. Johnson C, Jia Y, Wang C, et al. Role of caspase 2 in apoptotic signaling in primate and murine germ cells. Biol Reprod. 2008;79:806–14.

    Article  PubMed  CAS  Google Scholar 

  67. Basile A, Biziato D, Sherbet VG, et al. Hyperthermia inhibits cell proliferation and induces apoptosis: relative signaling status of P53, S100A4, and notch in heat sensitive and resistant cell lines. J Cell Biol. 2008;103:212–20.

    CAS  Google Scholar 

  68. Yamamoto CM, Sinha Hikim AP, Huynh PN, et al. Redistribution of Bax is an early step in an apoptotic pathway leading to germ cell death in rats, triggered by mild testicular hyperthermia. Biol Reprod. 2000;63:1683–90.

    Article  PubMed  CAS  Google Scholar 

  69. Shiraishi K, Naito K, Yoshida K. Vasectomy impairs spermatogenesis through germ cell apoptosis mediated by the p53-Bax pathway in rats. J Urol. 2001;166:1565–71.

    Article  PubMed  CAS  Google Scholar 

  70. Vydra N, Malusecka E, Jarzab M, et al. Spermatocyte-specific expression of constitutively active heat shock factor 1 induces HSP70i-resistant apoptosis in male germ cells. Cell Death Differ. 2006;13:212–22.

    Article  PubMed  CAS  Google Scholar 

  71. Yin Y, DeWolf WC, Morgentaler A. Experimental cyptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice. Biol Reprod. 1998;58:492–6.

    Article  PubMed  CAS  Google Scholar 

  72. Yin Y, Stahl BC, DeWolf WC, et al. p53-mediated germ cell quality control in spermatogenesis. Dev Biol. 1998;204:165–71.

    Article  PubMed  CAS  Google Scholar 

  73. Yin Y, Stahl BC, DeWolf WC, et al. P53 and Fas are sequential mechanism of testicular germ cell apoptosis. J Androl. 2002;23:64–70.

    PubMed  CAS  Google Scholar 

  74. Shiraishi K, Yoshida K, Fujimiya T, et al. Angiotensin II dependent testicular fibrosis and effects on spermatogenesis after vasectomy in the rat. J Urol. 2003;170:2104–8.

    Article  PubMed  CAS  Google Scholar 

  75. Shiraishi K, Naito K. Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol. 2007;178:1012–7.

    Article  PubMed  CAS  Google Scholar 

  76. Schwartz D, Goldfinger N, Rotter V. Expression of p53 protein in spermatogenesis is confined to the tetraploid pachytene primary spermatocytes. Oncogene. 1993;8:1487–94.

    PubMed  CAS  Google Scholar 

  77. Li W, Bao W, Ma J, et al. Metastasis tumor antigen 1 is involved in the resistance to heat stress-induced testicular apoptosis. FEBS Lett. 2008;582:869–73.

    Article  PubMed  CAS  Google Scholar 

  78. Sorimachi H, Ishiura S, Suzuki K. Structure and physiological function of calpains. Biochem J. 1997;328:721–32.

    PubMed  CAS  Google Scholar 

  79. Shiraishi K, Naito K, Yoshida K. Inhibition of calpain but not caspase protects the testis agaisnt injury after experimental testicular torsion of rat. Biol Reprod. 2000;63:1538–48.

    Article  PubMed  CAS  Google Scholar 

  80. Li FJ, Kondo T, Zhao QL, et al. Enhancement of hyperthermia-induced apoptosis by a free radical initiator, 2,2′-azobis(2-amidinopropane)dihydrochloride, in human histiocytic lymphoma U937 cells. Free Radic Res. 2001;35:281–99.

    Article  PubMed  CAS  Google Scholar 

  81. Lizama C, Lagos CF, Lagos-Cabré R, et al. Calpain inhibitors prevent p38 MAPK activation and germ cell apoptosis after heat stress in pubertal rat testes. J Cell Physiol. 2009;221:296–305.

    Article  PubMed  CAS  Google Scholar 

  82. Lu T, Xu Y, Mericle M, et al. Participation of conventional calpains in apoptosis. Biochim Biophys Acta. 2002;1590:16–26.

    Article  PubMed  CAS  Google Scholar 

  83. Somwaru L, Li S, Doglio L, et al. Heat-induced apoptosis of mouse meiotic cells is suppressed by ectopic expression of testis-specific calpastatin. J Androl. 2004;25:506–13.

    PubMed  CAS  Google Scholar 

  84. Zhang XS, Zhang ZH, Jin X, et al. Dedifferentiation of adult monkey Sertoli cells through activation of extracellularly regulated kinase 1/2 induced by heat treatment. Endocrinology. 2006;147:1237–45.

    Article  PubMed  CAS  Google Scholar 

  85. Reuter S, Gupta SC, Chaturvedi MM, et al. Oxidative stress, inflammation, and cancer: how they linked? Free Radic Biol Med. 2010;49:1603–16.

    Article  PubMed  CAS  Google Scholar 

  86. Adams SH. Uncoupling protein homologs: emerging views of physiological function. J Nutr. 2000;130:711–4.

    PubMed  CAS  Google Scholar 

  87. Zhang K, Shang Y, Liao S, et al. Uncoupling protein 2 protects testicular germ cells from hyperthermia-induced apoptosis. Biochem Biophys Res Commun. 2007;360:327–32.

    Article  PubMed  CAS  Google Scholar 

  88. Zhu H, Cui Y, Xie J, et al. Proteomic analysis of testis biopsies in men treated with transient scrotal hyperthermia revealed the potential targets for contraceptive development. Proteomics. 2010;10:3480–93.

    Article  PubMed  CAS  Google Scholar 

  89. Chowdhury DR, Small C, Wang Y, et al. Microarray-based analysis of cell-cycle gene expression during spermatogenesis in the mouse. Biol Reprod. 2010;83:663–75.

    Article  CAS  Google Scholar 

  90. Tanaka H, Fujisawa M, Okada H, et al. Assessment of germ-cell kinetics in the testes of patients with varicocele using image analysis of immunostained proliferating cell nuclear antigen. Br J Urol. 1996;78:769–71.

    Article  PubMed  CAS  Google Scholar 

  91. Shiraishi K, Naito K. Generation of 4-hydroxy-2-nonenal modified proteins in testis predicts improvement in spermatogenesis after varicocelectomy. Fertil Steril. 2006;86:233–5.

    Article  PubMed  CAS  Google Scholar 

  92. Fujisawa M, Matsumoto O, Kamidono S, et al. Changes of enzymes involved in DNA synthesis in the testes of cryptorchid rats. J Reprod Fertil. 1988;84:123–30.

    Article  PubMed  CAS  Google Scholar 

  93. Fujisawa M, Hayashi A, Okada H, et al. Enzymes involved in DNA synthesis in the testes are regulated by temperature in vitro. Eur Urol. 1997;31:237–42.

    PubMed  CAS  Google Scholar 

  94. Blow JJ, Tanaka TU. The chromosome cycle: coordinating replication and segregation. Second in the cycles review series. EMBO Rep. 2005;6:1028–34.

    Article  PubMed  CAS  Google Scholar 

  95. Wolgemuth DJ, Laurion E, Lele KM. Regulation of the mitotic and meiotic cell cycles in the male germline. Recent Prog Horm Res. 2002;57:75–101.

    Article  PubMed  CAS  Google Scholar 

  96. Zhang Y, Yang X, Cao H, et al. Heat stress induces Cdc2 protein decrease prior to mouse spermatogenic cell apoptosis. Acta Histochem. 2008;110:276–84.

    Article  PubMed  CAS  Google Scholar 

  97. King RW, Jackson PK, Kirschner MW. Mitosis in transition. Cell. 1994;79:563–71.

    Article  PubMed  CAS  Google Scholar 

  98. Shrivastava V, Peker M, Grosser E, et al. SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells. Reproduction. 2010;139:999–1010.

    Article  PubMed  CAS  Google Scholar 

  99. Zakeri ZF, Wolgemuth DJ, Hung CR. Identification and sequence analysis of a new member of the mouse HSP70 gene family and characterization of its unique cellular and developmental pattern of expression in the male germ line. Mol Cell Biol. 1988;8:2925–32.

    PubMed  CAS  Google Scholar 

  100. Eddy EM. Role of heat shock protein HSP70-2 in spermatogenesis. Rev Reprod. 1994;4:23–30.

    Article  Google Scholar 

  101. Kaushal N, Bansal MP. Dietary selenium variation-induced oxidative stress modulates CDC2/cyclin B1 expression and apoptosis of germ cells in mice testis. J Nutr Biochem. 2007;18:553–64.

    Article  PubMed  CAS  Google Scholar 

  102. Chandel NS, Vander Heiden MG, Thompson CB, et al. Redox regulation of p53 during hypoxia. Oncogene. 2000;19:3840–8.

    Article  PubMed  CAS  Google Scholar 

  103. Lindquist S. The heat-shock response. Annu Rev Biochem. 1986;55:1151–91.

    Article  PubMed  CAS  Google Scholar 

  104. Shimizu S, Saito M, Kinoshita Y, et al. Ischemic preconditioning and post-conditioning to decrease testicular torsion-detorsion injury. J Urol. 2009;182:1637–43.

    Article  PubMed  CAS  Google Scholar 

  105. Shiraishi K, Takihara H, Naito K. Testicular volume, scrotal temperature, and oxidative stress in fertile men with left varicocele. Fertil Steril. 2008;91:1388–91.

    Article  PubMed  Google Scholar 

  106. Bauche F, Fouchard M, Jegou B. Antioxidant system in rat testicular cells. FEBS Lett. 1994;349:392–6.

    Article  PubMed  CAS  Google Scholar 

  107. Gu W, Hecht NB. Developmental expression of glutathione peroxidase, catalase, and manganese superoxide dismutase mRNAs during spermatogenesis in the mouse. J Androl. 1996;17:256–62.

    PubMed  CAS  Google Scholar 

  108. Maines MD, Ewing JF. Stress response of the rat testis: in situ hybridization and immunohistochemical analysis of heme oxygenase-1 (HSP32) induction by hyperthermia. Biol Reprod. 1996;54:1070–9.

    Article  PubMed  CAS  Google Scholar 

  109. Mruk DD, Silvestrini B, Mo MY, et al. Antioxidant superoxide dismutase-a review: its function, regulation in the testis, and role in male fertility. Contraception. 2002;65:305–11.

    Article  PubMed  CAS  Google Scholar 

  110. Fujii J, Iuchi Y, Matsuki S, et al. Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues. Asian J Androl. 2003;5:231–42.

    PubMed  CAS  Google Scholar 

  111. Ishii T, Matsuki S, Iuchi Y, et al. Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress. Free Radic Res. 2005;39:697–705.

    Article  PubMed  CAS  Google Scholar 

  112. Okubo K, Nagahama K, Kamoto T, et al. GSTT1 and GSTM1 polymorphisms are associated with improvement in seminal findings after varicocelectomy. Fertil Steril. 2005;83:1579–80.

    Article  PubMed  CAS  Google Scholar 

  113. Zhu Y-F, Cui Y-G, Guo X-J, et al. Proteomic analysis of effect of hyperthermia on spermatogenesis in adult male mice. J Proteome Res. 2006;5:2217–25.

    Article  PubMed  CAS  Google Scholar 

  114. Li YC, Hu XQ, Xiao LJ, et al. An oligonucleotide microarray study on gene expression profile in mouse testis of experimental cryptorchidism. Front Biosci. 2006;11:2465–82.

    Article  PubMed  CAS  Google Scholar 

  115. McLean DJ, Russell LD, Griswold MD. Biological activity and enrichment of spermatogonial stem cells in vitamin A-deficient and hyperthermia-exposed testes from mice based on colonization following germ cell transplantation. Biol Reprod. 2002;66:1374–9.

    Article  PubMed  CAS  Google Scholar 

  116. Mines MD, Trakshel GM, Kutty RK. Characterization of two constitutive forms of rat liver microsomal heme oxygemase. Only one molecular form is inducible. J Biol Chem. 1986;261:411–9.

    Google Scholar 

  117. Ewing JF, Maines MD. Distribution of constitutive (HO-2) and heat inducible (HO-1) heme oxygenase isozymes in rat testis: HO-2 display stage-specific expression in spermatocytes. Endocrinology. 1995;136:2294–302.

    Article  PubMed  CAS  Google Scholar 

  118. Shiraishi K, Naito K. Increased expression of Leydig cell heme oxygenase-1 preserves spermatogenesis in varicocele. Hum Reprod. 2005;20:2608–13.

    Article  PubMed  CAS  Google Scholar 

  119. Cam K, Simsek F, Yuksel M, et al. The role of reactive oxygen species and apoptosis in the pathogenesis of varicocele in a rat model and efficiency of vitamin E treatment. Int J Androl. 2004;27:228–33.

    Article  PubMed  CAS  Google Scholar 

  120. Ross C, Morriss A, Khairy M, Khalaf Y, et al. A systemic review of the effect of oral antioxidants on male infertility. Reprod Biomed Online. 2010;20:711–23.

    Article  PubMed  CAS  Google Scholar 

  121. Ishikawa T, Fujioka H, Ishimura T, et al. Ghrelin expression in human testis and serum testosterone level. J Androl. 2006;28:320–4.

    Article  PubMed  CAS  Google Scholar 

  122. Dong MH, Kaunitz JD. Gastroduodenal mucosal defense. Curr Opin Gastroenterol. 2006;22:599–606.

    Article  PubMed  Google Scholar 

  123. Chung H, Kim E, Lee DH, et al. Ghrelin inhibits apoptosis in hypothalamin neuronal cells during oxygen-glucose deprivation. Endocrinology. 2007;148:148–59.

    Article  PubMed  CAS  Google Scholar 

  124. Piotrkowski B, Monzón CM, Pagotto RM, et al. Effects of heme oxygenase isozymes on Leydig cells steroidogenesis. J Endocrinol. 2009;203:155–65.

    Article  PubMed  CAS  Google Scholar 

  125. Allen RL, O’Brien DA, Jones CC, et al. Expression of heat shock proteins by isolated mouse spermatogenic cells. Mol Cell Biol. 1988;8:3260–6.

    PubMed  CAS  Google Scholar 

  126. Wu C. Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol. 1995;11:441–69.

    Article  PubMed  CAS  Google Scholar 

  127. Mizzen LA, Welch WJ. Characterization of the thermotolerant cell. I. Effects on protein synthesis activity and the regulation of heat-shock protein 70 expression. J Cell Biol. 1988;106:1105–16.

    Article  PubMed  CAS  Google Scholar 

  128. Feder ME, Hofmann GE. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol. 1999;61:243–82.

    Article  PubMed  CAS  Google Scholar 

  129. Sarge KD, Murphy SP, Morimoto RI. Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. Mol Cell Biol. 1993;13:1392–407.

    PubMed  CAS  Google Scholar 

  130. Beere HM. The stress of dying: the role of heat shock proteins in the regulation of apoptosis. J Cell Sci. 2004;117:2641–51.

    Article  PubMed  CAS  Google Scholar 

  131. Sreedhar AS, Csermely P. Heat shock proteins in the regulation of apoptosis: new strategies in tumor therapy: a comprehensive review. Pharmacol Ther. 2004;101:227–57.

    Article  PubMed  CAS  Google Scholar 

  132. Ogi S, Tanji N, Iseda T, et al. Expression of heat shock proteins in developing and degenerating rat testes. Arch Androl. 1999;43:163–71.

    Article  PubMed  CAS  Google Scholar 

  133. Rosario MO, Perkins SL, O’Brien DA, et al. Identification of the gene for the developmentally expressed 70 kDa heat-shock protein (P70) of mouse spermatogenic cells. Dev Biol. 1992;150:1–11.

    Article  PubMed  CAS  Google Scholar 

  134. Tsunekawa N, Matsumoto M, Tone S, Nishida T, Fujimoto H. The Hsp70 homolog gene, Hsc70t, is expressed under translational control during mouse spermiogenesis. Mol Reprod Dev. 1999;52:383–91.

    Article  PubMed  CAS  Google Scholar 

  135. Dix DJ. Hsp70 expression and function during gametogenesis. Cell Stress Chaperones. 1997;2:73–7.

    Article  PubMed  CAS  Google Scholar 

  136. Meinhardt A, Parvinen M, Bacher M, et al. Expression of mitochondrial heat shock protein 60 in distinct cell types and defined stages of rat seminiferous epithelium. Biol Reprod. 1995;52:798–807.

    Article  PubMed  CAS  Google Scholar 

  137. Lachance C, Fortier M, Thimon V, et al. Localization of Hsp60 and Grp78 in the human testis, epididymis and mature spermatozoa. Int J Androl. 2010;33:33–44.

    Article  PubMed  CAS  Google Scholar 

  138. Kumagai J, Fukuda J, Kodama H, et al. Germ cell-specific heat shock protein 105 binds to p53 in a temperature-sensitive manner in rat testis. Eur J Biochem. 2000;267:3073–8.

    Article  PubMed  CAS  Google Scholar 

  139. Adly MA, Assaf HA, Hussein MR. Heat shock protein 27 expression in the human testis showing normal and abnormal spermatogenesis. Cell Biol Int. 2008;32:1247–55.

    Article  PubMed  CAS  Google Scholar 

  140. Biggiogera M, Tanguay RM, Marin R, et al. Localization of heat shock proteins in mouse male germ cells: an immunoelectron microscopic study. Exp Cell Res. 1996;25:77–85.

    Article  Google Scholar 

  141. Yamano Y, Ohyama K, Ohta M, et al. Expression of small stress protein hsp20 gene in the maturing rat testis. J Vet Med Sci. 2005;67:1181–4.

    Article  PubMed  CAS  Google Scholar 

  142. Morimoto RI. Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev. 1998;12:3788–96.

    Article  PubMed  CAS  Google Scholar 

  143. Nakai A, Tanabe M, Kawazoe Y, et al. HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator. Mol Cell Biol. 1997;17:469–81.

    PubMed  CAS  Google Scholar 

  144. Nakai A. New aspect in the vertebrate heat shock factor system: HSF3 and HSF4. Cell Stress Chaperones. 1999;4:86–93.

    Article  PubMed  CAS  Google Scholar 

  145. Adachi M, Liu Y, Fujii K, et al. Oxidative stress impairs the heat stress response and delays unfolded protein recovery. PLoS One. 2009;4:e7719.

    Article  PubMed  CAS  Google Scholar 

  146. McMillan DR, Xiao X, Shao L, et al. Targeted disruption of heat shock transcription factor 1 abolishes thermotolerance and protection against heat-inducible apoptosis. J Biol Chem. 1998;273:7523–8.

    Article  PubMed  CAS  Google Scholar 

  147. Zhang Y, Huang L, Zhang J, et al. Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue-specific regulation for stress-inducible Hsp molecular chaperones. J Cell Biochem. 2002;86:376–93.

    Article  PubMed  CAS  Google Scholar 

  148. Wang G, Zhang J, Moskophidis D, et al. Targeted disruption of the heat shock transcription factor (hsf)-2 gene results in increased embryonic lethality, neuronal defects, and reduced spermatogenesis. Genesis. 2003;36:48–61.

    Article  PubMed  CAS  Google Scholar 

  149. Lecomte S, Desmots F, Le Masson F, et al. Roles of heat shock factor 1 and 2 in response to proteasome inhibition: consequence on p53 stability. Oncogene. 2010;29:4216–24.

    Article  PubMed  CAS  Google Scholar 

  150. Fujimoto M, Hayashida N, Katoh T, et al. A novel mouse HSF3 has the potential to activate nonclassical heat-shock genes during heat shock. Mol Biol Cell. 2010;21:106–16.

    Article  PubMed  CAS  Google Scholar 

  151. Ferlin A, Arredi B, Speltra E, et al. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab. 2007;92:762–70.

    Article  PubMed  CAS  Google Scholar 

  152. Ferlin A, Speltra E, Patassini C, et al. Heat shock protein and heat shock factor expression in sperm: relation to oligozoospermia and varicocele. J Urol. 2010;183:1248–52.

    Article  PubMed  CAS  Google Scholar 

  153. Koksal IT, Tefekli A, Usta M, et al. The role of reactive oxygen species in testicular dysfunction associated with varicocele. BJU Int. 2000;86:549–52.

    Article  PubMed  CAS  Google Scholar 

  154. Widlak W, Vydra N, Malusecka E, et al. Heat shock transcription factor 1 down-regulates spermatocyte-specicic 70 kDa heat shock protein expression prior to the induction of apoptosis in mouse testes. Genes Cells. 2007;12:487–99.

    Article  PubMed  CAS  Google Scholar 

  155. Rhynes WE, Ewing LL. Testicular endocrine function in Hereford bulls exposed to high ambient temperature. Endocrinology. 1973;92:509–15.

    Article  PubMed  CAS  Google Scholar 

  156. Wettemann RP, Desjardins C. Testicular function in boars exposed to elevated ambient temperature. Biol Reprod. 1979;20:235–41.

    Article  PubMed  CAS  Google Scholar 

  157. Chiba K, Ishikawa T, Yamaguchi K, et al. The efficacy of adult orchiopexy as a treatment of male infertility: our experience of 20 cases. Fertil Steril. 2009;92:1337–9.

    Article  PubMed  Google Scholar 

  158. Matsuki S, Iuchi Y, Ikeda Y, et al. Supression of cytochrome c release and apoptosis in tetes with heat stress by minocycline. Biochem Biophys Res Commun. 2003;312:843–9.

    Article  PubMed  CAS  Google Scholar 

  159. Zhang ZH, Hu ZY, Song XX, et al. Disrupted expression of intermediate filaments in the testis of rhesus monkey after experimental cryptorchidism. Int J Androl. 2004;27:234–9.

    Article  PubMed  Google Scholar 

  160. Guo J, Tao SX, Chen M, et al. Heat treatment induces liver receptor homolog-1 expression in monkey and rat Sertoli cells. Endocrinology. 2007;148:1255–65.

    Article  PubMed  CAS  Google Scholar 

  161. Chen M, Cai H, Yang JL, et al. Effect of heat stress on expression of junction-associated molecules and upstream factors androgen receptor and Wilms’ tumor 1 in monkey Sertoli cells. Endocrinology. 2008;149:4871–82.

    Article  PubMed  CAS  Google Scholar 

  162. Meng J, Holdcraft RW, Shima JE, et al. Androgens regulate the permeability of the blood–testis barrier. Proc Natl Acad Sci USA. 2005;102:16696–700.

    Article  PubMed  CAS  Google Scholar 

  163. Cai H, Ren Y, Li X-X, et al. Scrotal heat stress causes a transient alteration in tight junctions and induction of TGF-β expression. Int J Androl. 2011;34:352–62.

    Article  PubMed  CAS  Google Scholar 

  164. Siu ER, Mruk DD, Porto CS, et al. Cadmium-induced testicular injury. Toxicol Appl Pharmacol. 2009;238:240–9.

    Article  PubMed  CAS  Google Scholar 

  165. Takada T, Kitamura M, Matsumiya K, et al. Infrared thermometry for rapid, noninvasive detection of reflux of spermatic vein in varicocele. J Urol. 1996;156:1652–4.

    Article  PubMed  CAS  Google Scholar 

  166. Jung A, Leonhardt F, Schill WB, et al. Influence of the type of undertrousers and physical activity on scrotal temperatures. Hum Reprod. 2005;20:1022–7.

    Article  PubMed  CAS  Google Scholar 

  167. Hjollund NH, Storgaard L, Ernst E, et al. The relation between daily activities and scrotal temperature. Reprod Toxicol. 2002;16:209–14.

    Article  PubMed  CAS  Google Scholar 

  168. Yamaguchi M, Sakatoku J, Takihara H. The application of intrascrotal deep body temperature measurement for the noninvasive diagnosis of varicoceles. Fertil Steril. 1989;52:295–301.

    PubMed  CAS  Google Scholar 

  169. Takihara H, Yamaguchi M, Baba Y, et al. Deep body intrascrotal thermometer: theory and methodology. Adv Exp Med Biol. 1991;286:115–9.

    Article  PubMed  CAS  Google Scholar 

  170. Bengoudifa B, Mieusset R. Thermal asymmetry of the human scrotum. Hum Reprod. 2007;22:2178–82.

    Article  PubMed  CAS  Google Scholar 

  171. Jockenhövel F, Gräwe A, Nieschlag E. A portable digital data recorder for long-term monitoring of scrotal temperatures. Fertil Steril. 1990;54:694–700.

    PubMed  Google Scholar 

  172. Thonneau P, Bujan L, Multigner L, et al. Occupational heat exposure and male fertility: a review. Hum Reprod. 1998;13:2122–5.

    Article  PubMed  CAS  Google Scholar 

  173. Ishikawa T, Fujioka H, Ishimura T, et al. Increased testicular 8-hydroxy-2′-deoxyguanosine in patients with varicocele. BJU Int. 2007;100:863–6.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Koji Shiraishi MD, PhD .

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Shiraishi, K. (2012). Heat and Oxidative Stress in the Germ Line. In: Agarwal, A., Aitken, R., Alvarez, J. (eds) Studies on Men's Health and Fertility. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-61779-776-7_8

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