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Heat stress response of male germ cells

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Abstract

The vast majority of mammalian testes are located outside the body cavity for proper thermoregulation. Heat has an adverse effect on mammalian spermatogenesis and eventually leads to sub- or infertility. Recent studies have provided insights into the molecular response of male germ cells to high temperatures. Here, we review the effects of heat on male germ cells and discuss the mechanisms underlying germ cell loss and impairment. We also discuss the role of translational control in male germ cells as a potential protective mechanism against heat-induced germ cell apoptosis.

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References

  1. Sharpe RM (1994) Regulation of spermatogenesis. In: Knobil E, Neil JD (eds) The physiology of reproduction, 2nd edn. Raven, New York, pp 1363–1434

    Google Scholar 

  2. Cooke HJ, Saunders PT (2002) Mouse models of male infertility. Nat Rev Genet 3:790–801

    PubMed  CAS  Google Scholar 

  3. Clermont Y (1963) The cycle of the seminiferous epithelium in man. Am J Anat 112:35–51

    PubMed  CAS  Google Scholar 

  4. Fukui N (1923) Action of body temperature on the testicle. Jpn Med World 3:160–163

    Google Scholar 

  5. Frankenhuis MT, Wensing CJ (1979) Induction of spermatogenesis in the naturally cryptorchid pig. Fertil Steril 31:428–433

    PubMed  CAS  Google Scholar 

  6. Hutson JM, Hasthorpe S, Heyns CF (1997) Anatomical and functional aspects of testicular descent and cryptorchidism. Endocr Rev 18:259–280

    PubMed  CAS  Google Scholar 

  7. Moore CR (1924) Properties of the gonads as controllers of somatic and psychical characteristics. VI. Testicular reactions in experimental cryptorchidism. Am J Anat 34:269–316

    Google Scholar 

  8. Moore CR, Quick WJ (1924) The scrotum as a temperature regulator for the testis. Am J Physiol 68:70–79

    Google Scholar 

  9. Harrison RG, Weiner JS (1948) Abdomino-testicular temperature gradients. J Physiol 107:48–49

    Google Scholar 

  10. Waites GM, Moule GR (1961) Relation of vascular heat exchange to temperature regulation in the testis of the ram. J Reprod Fertil 2:213–224

    PubMed  CAS  Google Scholar 

  11. Zorgniotti AA (1991) Temperature and environmental effects on the testis. Plenum, New York

    Google Scholar 

  12. Brito LF, Silva AE, Barbosa RT, Kastelic JP (2004) Testicular thermoregulation in Bos indicus, crossbred and Bos taurus bulls: relationship with scrotal, testicular vascular cone and testicular morphology, and effects on semen quality and sperm production. Theriogenology 61:511–528

    PubMed  Google Scholar 

  13. Rommel SA, Pabst DA, McLellan WA, Mead JG, Potter CW (1992) Anatomical evidence for a countercurrent heat exchanger associated with dolphin testes. Anat Rec 232:150–156

    PubMed  CAS  Google Scholar 

  14. Rommel SA, Pabst DA, McLellan WA, Willimas TM, Freidl WA (1994) Temperature regulation of the testes of the bottlenose dolphin (Tursiops truncatus): evidence from colonic temperatures. J Comp Physiol B 164:130–134

    PubMed  CAS  Google Scholar 

  15. Rommel SA, Early GA, Matassa KA, Pabst DA, McLellan WA (1995) Venous structures associated with thermoregulation of phocid seal reproductive organs. Anat Rec 243:390–402

    PubMed  CAS  Google Scholar 

  16. Pabst DA, Rommel SA, McLellan WA, Williams TM, Rowles TK (1995) Thermoregulation of the intra-abdominal testes of the bottlenose dolphin (Tursiops truncatus) during exercise. J Exp Biol 198:221–226

    PubMed  CAS  Google Scholar 

  17. Setchell BP (1998) The Parkes lecture. Heat and the testis. J Reprod Fertil 114:179–194

    PubMed  CAS  Google Scholar 

  18. Morgentaler A, Stahl BC, Yin Y (1999) Testis and temperature: an historical, clinical and research perspective. J Androl 20:189–195

    PubMed  CAS  Google Scholar 

  19. Casady RB, Myers RM, Legates JE (1953) The effect of exposure to high ambient temperature on spermatogenesis in the dairy bull. J Dairy Sci 36:14–19

    Google Scholar 

  20. Collins P, Lacy D (1969) Studies on the structure and function of the mammalian testis. II. Cytological and histochemical observations on the testis of the rat after a single exposure to heat applied for different lengths of time. Proc R Soc Lond B 172:17–38

    PubMed  CAS  Google Scholar 

  21. French DJ, Leeb CS, Fahrion SL, Law OT, Jecht EW (1973) Self-induced scrotal hyperthermia in man followed by decrease in sperm output. A preliminary report. Andrologie 5:311–316

    PubMed  CAS  Google Scholar 

  22. Wettemann RP, Wells ME, Omtvedt IT, Pope CE, Turman EJ (1976) Influence of elevated ambient temperature on reproductive performance of boars. J Anim Sci 42:664–669

    PubMed  CAS  Google Scholar 

  23. Hand JW, Walker H, Hornsey S, Field SB (1979) Effects of hyperthermia on the mouse testis and its response to X-rays, as assayed by weight loss. Int J Radiat Biol Relat Stud Phys Chem Med 35:521–528

    PubMed  CAS  Google Scholar 

  24. Freidman R, Scott M, Heath SE, Hughes JP, Daels PF, Tran TQ (1991) The effects of increased testicular temperature on spermatogenesis in the stallion. J Reprod Fertil 44:127–134

    CAS  Google Scholar 

  25. Mieusset R, Quintana Casares P, Sanchez Partida LG, Sowerbutts SF, Zupp JL, Setchell BP (1992) Effects of heating the testes and epididymides of rams by scrotal insulation on fertility and embryonic mortality in ewes inseminated with frozen semen. J Reprod Fertil 94:337–343

    PubMed  CAS  Google Scholar 

  26. Mieusset R, Bujan L (1995) Testicular heating and its possible contributions to male infertility: a review. Int J Androl 18:169–184

    PubMed  CAS  Google Scholar 

  27. Zhou XC, Han XB, Hu ZY, Zhou RJ, Liu YX (2001) Expression of Hsp70-2 in unilateral cryptorchid testis of rhesus monkey during germ cell apoptosis. Endocrine 16:89–95

    PubMed  CAS  Google Scholar 

  28. Schwalm A, Gauly M, Erhardt G, Bergmann M (2007) Changes in testicular histology and sperm quality in llamas (Lama glama), following exposure to high ambient temperature. Theriogenology 67:1316–1323

    PubMed  CAS  Google Scholar 

  29. Setchell BP (2006) The effect of heat on the testes of mammals. Anim Reprod 3:81–91

    Google Scholar 

  30. Shikone T, Billig H, Hsueh AJ (1994) Experimentally induced cryptorchidism increases apoptosis in rat testis. Biol Reprod 51:865–872

    PubMed  CAS  Google Scholar 

  31. Ohta Y, Nishikawa A, Fukazawa Y, Urushitani H, Matsuzawa A, Nishina Y, Iguchi T (1996) Apoptosis in adult mouse testis induced by experimental cryptorchidism. Acta Anat 157:195–204

    PubMed  CAS  Google Scholar 

  32. Yin Y, Hawkins KL, DeWolf WC, Morgentaler A (1997) Heat stress causes testicular germ cell apoptosis in adult mice. J Androl 18:159–165

    PubMed  CAS  Google Scholar 

  33. Lue YH, Hikim AP, Swerdloff RS, Im P, Taing KS, Bui T, Leung A, Wang C (1999) Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology 140:1709–1717

    PubMed  CAS  Google Scholar 

  34. Rockett JC, Mapp FL, Garges JB, Luft JC, Mori C, Dix DJ (2001) Effects of hyperthermia on spermatogenesis, apoptosis, gene expression, and fertility in adult male mice. Biol Reprod 65:229–239

    PubMed  CAS  Google Scholar 

  35. Ikeda M, Kodama H, Fukuda J, Shimizu Y, Murata M, Kumagai J, Tanaka T (1999) Role of radical oxygen species in rat testicular germ cell apoptosis induced by heat stress. Biol Reprod 61:393–399

    PubMed  CAS  Google Scholar 

  36. Socher SA, Yin Y, Dewolf WC, Morgentaler A (1997) Temperature-mediated germ cell loss in the testis is associated with altered expression of the cell-cycle regulator p53. J Urol 157:1986–1989

    PubMed  CAS  Google Scholar 

  37. Zhang XS, Yuan JX, Liu T, Lue YH, Jin X, Tao SX, Hu ZY, Hikim AP, Swerdloff RS, Wang C, Liu YX (2006) Expression of orphan receptors TR2, TR3, TR4, and p53 in heat-treated testis of cynomolgus monkeys (Macaca fascicularis). J Androl 27:405–413

    PubMed  CAS  Google Scholar 

  38. Absalan F, Movahedin M, Mowla SJ (2010) Germ cell apoptosis induced by experimental cryptorchidism is mediated by molecular pathways in mouse testis. Andrologia 42:5–12

    PubMed  CAS  Google Scholar 

  39. Yin Y, DeWolf WC, Morgentaler A (1998) Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice. Biol Reprod 58:492–496

    PubMed  CAS  Google Scholar 

  40. Yin Y, Stahl BC, DeWolf WC, Morgentaler A (2002) p53 and Fas are sequential mechanisms of testicular germ cell apoptosis. J Androl 23:64–70

    PubMed  CAS  Google Scholar 

  41. Sinha Hikim AP, Lue Y, Yamamoto CM, Vera Y, Rodriguez S, Yen PH, Soeng K, Wang C, Swerdloff RS (2003) Key apoptotic pathways for heat-induced programmed germ cell death in the testis. Endocrinology 144:3167–3175

    Google Scholar 

  42. Sinha Hikim AP, Lue Y, Diaz-Romero M, Yen PH, Wang C, Swerdloff RS (2003) Deciphering the pathways of germ cell apoptosis in the testis. J Steroid Biochem Mol Biol 85:175–182

    PubMed  CAS  Google Scholar 

  43. Vera Y, Diaz-Romero M, Rodriguez S, Lue Y, Wang C, Swerdloff RS, Sinha Hikim AP (2004) Mitochondria-dependent pathway is involved in heat-induced male germ cell death: lessons from mutant mice. Biol Reprod 70:1534–1540

    PubMed  CAS  Google Scholar 

  44. Yamamoto CM, Sinha Hikim AP, Huynh PN, Shapiro B, Lue Y, Salameh WA, Wang C, Swerdloff RS (2000) 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 63:1683–1690

    PubMed  CAS  Google Scholar 

  45. Jia Y, Castellanos J, Wang C, Sinha-Hikim I, Lue Y, Swerdloff RS, Sinha-Hikim AP (2009) Mitogen-activated protein kinase signaling in male germ cell apoptosis in the rat. Biol Reprod 80:771–780

    PubMed  CAS  Google Scholar 

  46. Matsuki S, Iuchi Y, Ikeda Y, Sasagawa I, Tomita Y, Fujii J (2003) Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline. Biochem Biophys Res Commun 312:843–849

    PubMed  CAS  Google Scholar 

  47. Vera Y, Rodriguez S, Castanares M, Lue Y, Atienza V, Wang C, Swerdloff RS, Sinha Hikim AP (2005) Functional role of caspases in heat-induced testicular germ cell apoptosis. Biol Reprod 72:516–522

    PubMed  CAS  Google Scholar 

  48. Lue Y, Sinha Hikim AP, Wang C, Leung A, Swerdloff RS (2003) Functional role of inducible nitric oxide synthase in the induction of male germ cell apoptosis, regulation of sperm number, and determination of testes size: evidence from null mutant mice. Endocrinology 144:3092–3100

    PubMed  CAS  Google Scholar 

  49. DeFoor WR, Kuan CY, Pinkerton M, Sheldon CA, Lewis AG (2004) Modulation of germ cell apoptosis with a nitric oxide synthase inhibitor in a murine model of congenital cryptorchidism. J Urol 172:1731–1735

    PubMed  CAS  Google Scholar 

  50. Ishikawa T, Kondo Y, Goda K, Fujisawa M (2005) Overexpression of endothelial nitric oxide synthase in transgenic mice accelerates testicular germ cell apoptosis induced by experimental cryptorchidism. J Androl 26:281–288

    PubMed  CAS  Google Scholar 

  51. Johnson C, Jia Y, Wang C, Lue YH, Swerdloff RS, Zhang XS, Hu ZY, Li YC, Liu YX, Hikim AP (2008) Role of caspase 2 in apoptotic signaling in primate and murine germ cells. Biol Reprod 79:806–814

    PubMed  CAS  Google Scholar 

  52. Russell LD, Ettlin RA, Sinha-Hikim AP, Clegg ED (1990) Histological and histopathological evaluation of the testis. Cache River, Clearwater

    Google Scholar 

  53. Henriksén K, Hakovirta H, Parvinen M (1995) In situ quantification of stage-specific apoptosis in the rat seminiferous epithelium: effects of short-term experimental cryptorchidism. Int J Androl 18:256–262

    PubMed  Google Scholar 

  54. Kim B, Cooke HJ, Rhee K (2012) DAZL is essential for stress granule formation implicated in germ cell survival upon heat stress. Development 139:568–578

    PubMed  CAS  Google Scholar 

  55. Steinberger E, Dixon WJ (1959) Some observations on the effect of heat on the testicular germinal epithelium. Fert Steril 10:578–595

    Google Scholar 

  56. Loughlin KR, Manson K, Foreman R, Schwartz B, Heuttner P (1991) The effect of intermittent scrotal hyperthermia on the Sprague-Dawley rat testicle. Adv Exp Med Biol 286:183–185

    PubMed  CAS  Google Scholar 

  57. Karabinus DS, Vogler CJ, Saacke RG, Evenson DP (1997) Chromatin structural changes in sperm after scrotal insulation of Holstein bulls. J Androl 18:549–555

    PubMed  CAS  Google Scholar 

  58. Sailer BL, Sarkar LJ, Bjordahl JA, Jost LK, Evenson DP (1997) Effects of heat stress on mouse testicular cells and sperm chromatin structure. J Androl 18:294–301

    PubMed  CAS  Google Scholar 

  59. Banks S, King SA, Irvine DS, Saunders PT (2005) Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa. Reproduction 129:505–514

    PubMed  CAS  Google Scholar 

  60. Paul C, Murray AA, Spears N, Saunders PT (2008) A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction 136:73–84

    PubMed  CAS  Google Scholar 

  61. Garriott ML, Chrisman CL (1980) Hyperthermia induced dissociation of the X-Y bivalent in mice. Environ Mutagen 2:465–471

    PubMed  CAS  Google Scholar 

  62. van Zelst SJ, Zupp JL, Hayman DL, Setchell BP (1995) X-Y chromosome dissociation in mice and rats exposed to increased testicular or environmental temperatures. Reprod Fertil Dev 7:1117–1121

    PubMed  Google Scholar 

  63. Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, Irvine DS (1998) Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 59:1037–1046

    PubMed  CAS  Google Scholar 

  64. Twigg J, Fulton N, Gomez E, Irvine DS, Aitken RJ (1998) Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Hum Reprod 13:1429–1436

    PubMed  CAS  Google Scholar 

  65. Aitken RJ, Krausz C (2001) Oxidative stress, DNA damage and the Y chromosome. Reproduction 122:497–506

    PubMed  CAS  Google Scholar 

  66. Aitken RJ, Baker MA (2006) Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol 250:66–69

    PubMed  CAS  Google Scholar 

  67. Ahotupa M, Huhtaniemi I (1992) Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally cryptorchid rat testis. Biol Reprod 46:1114–1118

    PubMed  CAS  Google Scholar 

  68. Li YC, Hu XQ, Xiao LJ, Hu ZY, Guo J, Zhang KY, Song XX, Liu YX (2006) An oligonucleotide microarray study on gene expression profile in mouse testis of experimental cryptorchidism. Front Biosci 11:2465–2482

    PubMed  CAS  Google Scholar 

  69. Paul C, Teng S, Saunders PT (2009) A single, mild, transient scrotal heat stress causes hypoxia and oxidative stress in mouse testes, which induces germ cell death. Biol Reprod 80:913–919

    PubMed  CAS  Google Scholar 

  70. Kumagai A, Kodama H, Kumagai J, Fukuda J, Kawamura K, Tanikawa H, Sato N, Tanaka T (2002) Xanthine oxidase inhibitors suppress testicular germ cell apoptosis induced by experimental cryptorchidism. Mol Hum Reprod 8:118–123

    PubMed  CAS  Google Scholar 

  71. Ishii T, Matsuki S, Iuchi Y, Okada F, Toyosaki S, Tomita Y, Ikeda Y, Fujii J (2005) Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress. Free Radic Res 39:697–705

    PubMed  CAS  Google Scholar 

  72. Paul C, Melton DW, Saunders PT (2008) Do heat stress and deficits in DNA repair pathways have a negative impact on male fertility? Mol Hum Reprod 14:1–8

    PubMed  CAS  Google Scholar 

  73. Bellvé AR (1972) Viability and survival of mouse embryos following parental exposure to high temperature. J Reprod Fertil 30:71–81

    PubMed  Google Scholar 

  74. Bellvé AR (1973) Development of mouse embryos with abnormalities induced by parental heat stress. J Reprod Fertil 35:393–403

    PubMed  Google Scholar 

  75. Setchell BP, D’Occhio MJ, Hall MJ, Laurie MS, Tucker MJ, Zupp JL (1988) Is embryonic mortality increased in normal female rats mated to subfertile males? J Reprod Fertil 82:567–574

    PubMed  CAS  Google Scholar 

  76. Jannes P, Spiessens C, Van der Auwera I, D’Hooghe T, Verhoeven G, Vanderschueren D (1998) Male subfertility induced by acute scrotal heating affects embryo quality in normal female mice. Hum Reprod 13:372–375

    PubMed  CAS  Google Scholar 

  77. Setchell BP, Ekpe G, Zupp JL, Surani MA (1998) Transient retardation in embryo growth in normal female mice made pregnant by males whose testes had been heated. Hum Reprod 13:342–347

    PubMed  CAS  Google Scholar 

  78. Zhu BK, Setchell BP (2004) Effects of paternal heat stress on the in vivo development of preimplantation embryos in the mouse. Reprod Nutr Dev 44:617–629

    PubMed  Google Scholar 

  79. Yaeram J, Setchell BP, Maddocks S (2006) Effect of heat stress on the fertility of male mice in vivo and in vitro. Reprod Fertil Dev 18:647–653

    PubMed  CAS  Google Scholar 

  80. Walters AH, Eyestone WE, Saacke RG, Pearson RE, Gwazdauskas FC (2005) Bovine embryo development after IVF with spermatozoa having abnormal morphology. Theriogenology 63:1925–1937

    PubMed  CAS  Google Scholar 

  81. Walters AH, Saacke RG, Pearson RE, Gwazdauskas FC (2006) Assessment of pronuclear formation following in vitro fertilization with bovine spermatozoa obtained after thermal insulation of the testis. Theriogenology 65:1016–1028

    PubMed  CAS  Google Scholar 

  82. Zhu B, Walker SK, Oakey H, Setchell BP, Maddocks S (2004) Effect of paternal heat stress on the development in vitro of preimplantation embryos in the mouse. Andrologia 36:384–394

    PubMed  CAS  Google Scholar 

  83. Hagenas L, Ritzen EM (1975) Impaired Sertoli cell function in experimental cryptorchidism in the rat. Mol Cell Endocrinol 4:25–34

    PubMed  CAS  Google Scholar 

  84. Karpe B, Plöen L, Hagenäs L, Ritzén EM (1981) Recovery of testicular functions after surgical treatment of experimental cryptorchidism in the rat. Int J Androl 4:145–160

    PubMed  CAS  Google Scholar 

  85. Zhang ZH, Hu ZY, Song XX, Xiao LJ, Zou RJ, Han CS, Liu YX (2004) Disrupted expression of intermediate filaments in the testis of rhesus monkey after experimental cryptorchidism. Int J Androl 27:234–239

    PubMed  Google Scholar 

  86. Zhang XS, Zhang ZH, Jin X, Wei P, Hu XQ, Chen M, Lu CL, Lue YH, Hu ZY, Sinha Hikim AP, Swerdloff RS, Wang C, Liu YX (2006) Dedifferentiation of adult monkey Sertoli cells through activation of extracellularly regulated kinase 1/2 induced by heat treatment. Endocrinology 147:1237–1245

    PubMed  CAS  Google Scholar 

  87. Guo J, Tao SX, Chen M, Shi YQ, Zhang ZQ, Li YC, Zhang XS, Hu ZY, Liu YX (2007) Heat treatment induces liver receptor homolog-1 expression in monkey and rat Sertoli cells. Endocrinology 148:1255–1265

    PubMed  CAS  Google Scholar 

  88. Chen M, Cai H, Yang JL, Lu CL, Liu T, Yang W, Guo J, Hu XQ, Fan CH, Hu ZY, Gao F, Liu YX (2008) Effect of heat stress on expression of junction-associated molecules and upstream factors androgen receptor and Wilms’ tumor 1 in monkey Sertoli cells. Endocrinology 149:4871–4882

    PubMed  CAS  Google Scholar 

  89. Cai H, Ren Y, Li XX, Yang JL, Zhang CP, Chen M, Fan CH, Hu XQ, Hu ZY, Gao F, Liu YX (2011) Scrotal heat stress causes a transient alteration in tight junctions and induction of TGF-β expression. Int J Androl 34:352–362

    PubMed  Google Scholar 

  90. Aktas C, Kanter M (2009) A morphological study on Leydig cells of scrotal hyperthermia applied rats in short-term. J Mol Histol 40:31–39

    PubMed  Google Scholar 

  91. Kanter M, Aktas C (2009) Effects of scrotal hyperthermia on Leydig cells in long-term: a histological, immunohistochemical and ultrastructural study in rats. J Mol Histol 40:123–130

    PubMed  Google Scholar 

  92. Maines MD, Ewing JF (1996) Stress response of the rat testis: in situ hydridization and immunohistochemical analysis of heme oxygenase-1 (HSP32) induction by hyperthermia. Biol Reprod 54:1070–1079

    PubMed  CAS  Google Scholar 

  93. Meistrich ML, Eng VW, Loir M (1973) Temperature effects on the kinetics of spermatogenesis in the mouse. Cell Tissue Kinet 6:379–393

    PubMed  CAS  Google Scholar 

  94. Parvinen M, Pelto-Huikko M, Söder O, Schultz R, Kaipia A, Mali P, Toppari J, Hakovirta H, Lönnerberg P, Ritzén EM, Ebendal T, Olson L, Hökfelt T, Persson H (1992) Expression of beta-nerve growth factor and its receptor in rat seminiferous epithelium: specific function at the onset of meiosis. J Cell Biol 117:629–641

    PubMed  CAS  Google Scholar 

  95. Setchell BP, Waites GM (1972) The effects of local heating of the testis on the flow and composition of rete testis fluid in the rat, with some observations on the effects of age and unilateral castration. J Reprod Fertil 30:225–233

    PubMed  CAS  Google Scholar 

  96. Setchell BP, Tao L, Zupp JL (1996) The penetration of chromium-EDTA from blood plasma into various compartments of rat testes as an indicator of function of the blood-testis barrier after exposure of the testes to heat. J Reprod Fertil 106:125–133

    PubMed  CAS  Google Scholar 

  97. Setchell BP, Plöen L, Ritzen EM (2001) Reduction of long-term effects of local heating of the testis by treatment of rats with a GnRH agonist and an anti-androgen. Reproduction 122:255–263

    PubMed  CAS  Google Scholar 

  98. Setchell BP, Plöen L, Ritzen EM (2002) Effect of local heating of rat testes after suppression of spermatogenesis by pretreatment with a GnRH agonist and an anti-androgen. Reproduction 124:133–140

    PubMed  CAS  Google Scholar 

  99. Zhu YF, Cui YG, Guo XJ, Wang L, Bi Y, Hu YQ, Zhao X, Liu Q, Huo R, Lin M, Zhou ZM, Sha JH (2006) Proteomic analysis of effect of hyperthermia on spermatogenesis in adult male mice. J Proteome Res 5:2217–2225

    PubMed  CAS  Google Scholar 

  100. Zhu H, Cui Y, Xie J, Chen L, Chen X, Guo X, Zhu Y, Wang X, Tong J, Zhou Z, Jia Y, Lue YH, Hikim AS, Wang C, Swerdloff RS, Sha J (2010) Proteomic analysis of testis biopsies in men treated with transient scrotal hyperthermia reveals the potential targets for contraceptive development. Proteomics 10:3480–3493

    PubMed  CAS  Google Scholar 

  101. Riedl SJ, Shi Y (2004) Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 5:897–907

    PubMed  CAS  Google Scholar 

  102. Mu X, Liu Y, Collins LL, Kim E, Chang C (2000) The p53/retinoblastoma-mediated repression of testicular orphan receptor-2 in the rhesus monkey with cryptorchidism. J Biol Chem 275:23877–23883

    PubMed  CAS  Google Scholar 

  103. Hayashi T, Yoshida S, Yoshinaga A, Ohno R, Ishii N, Yamada T (2006) HtrA2 is up-regulated in the rat testis after experimental cryptorchidism. Int J Urol 13:157–164

    PubMed  CAS  Google Scholar 

  104. Hayashida N, Inouye S, Fujimoto M, Tanaka Y, Izu H, Takaki E, Ichikawa H, Rho J, Nakai A (2006) A novel HSF1-mediated death pathway that is suppressed by heat shock proteins. EMBO J 25:4773–4783

    PubMed  CAS  Google Scholar 

  105. Jia Y, Hikim AP, Lue YH, Swerdloff RS, Vera Y, Zhang XS, Hu ZY, Li YC, Liu YX, Wang C (2007) Signaling pathways for germ cell death in adult cynomolgus monkeys (Macaca fascicularis) induced by mild testicular hyperthermia and exogenous testosterone treatment. Biol Reprod 77:83–92

    PubMed  CAS  Google Scholar 

  106. Guo J, Jia Y, Tao SX, Li YC, Zhang XS, Hu ZY, Chiang N, Lue YH, Hikim AP, Swerdloff RS, Wang C, Liu YX (2009) Expression of nitric oxide synthase during germ cell apoptosis in testis of cynomolgus monkey after testosterone and heat treatment. J Androl 30:190–199

    PubMed  CAS  Google Scholar 

  107. Li W, Wu ZQ, Zhao J, Guo SJ, Li Z, Feng X, Ma L, Zhang JS, Liu XP, Zhang YQ (2011) Transient protection from heat-stress induced apoptotic stimulation by metastasis-associated protein 1 in pachytene spermatocytes. PLoS ONE 6:e26013

    PubMed  CAS  Google Scholar 

  108. Liu F, Xu ZL, Qian XJ, Qiu WY, Huang H (2011) Expression of Hsf1, Hsf2, and Phlda1 in cells undergoing cryptorchid-induced apoptosis in rat testes. Mol Reprod Dev 78:283–291

    PubMed  CAS  Google Scholar 

  109. Lizama C, Lagos CF, Lagos-Cabré R, Cantuarias L, Rivera F, Huenchuñir P, Pérez-Acle T, Carrión F, Moreno RD (2009) Calpain inhibitors prevent p38 MAPK activation and germ cell apoptosis after heat stress in pubertal rat testes. J Cell Physiol 221:296–305

    PubMed  CAS  Google Scholar 

  110. Richter K, Haslbeck M, Buchner J (2010) The heat shock response: life on the verge of death. Mol Cell 40:253–266

    PubMed  CAS  Google Scholar 

  111. Sarge KD, Cullen KE (1997) Regulation of hsp expression during rodent spermatogenesis. Cell Mol Life Sci 53:191–197

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  113. Dix DJ, Allen JW, Collins BW, Mori C, Nakamura N, Poorman-Allen P, Goulding EH, Eddy EM (1996) Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proc Natl Acad Sci USA 93:3264–3268

    PubMed  CAS  Google Scholar 

  114. Zakeri ZF, Welch WJ, Wolgemuth DJ (1990) Characterization and inducibility of hsp 70 proteins in the male mouse germ line. J Cell Biol 111:1785–1792

    PubMed  CAS  Google Scholar 

  115. Sarge KD (1995) Male germ cell-specific alteration in temperature set point of the cellular stress response. J Biol Chem 270:18745–18748

    PubMed  CAS  Google Scholar 

  116. Kumagai J, Fukuda J, Kodama H, Murata M, Kawamura K, Itoh H, Tanaka T (2000) Germ cell-specific heat shock protein 105 binds to p53 in a temperature-sensitive manner in rat testis. Eur J Biochem 267:3073–3078

    PubMed  CAS  Google Scholar 

  117. Zhang XS, Lue YH, Guo SH, Yuan JX, Hu ZY, Han CS, Hikim AP, Swerdloff RS, Wang C, Liu YX (2005) Expression of HSP105 and HSP60 during germ cell apoptosis in the heat-treated testes of adult cynomolgus monkeys (Macaca fascicularis). Front Biosci 10:3110–3121

    PubMed  CAS  Google Scholar 

  118. Widlak W, Vydra N, Malusecka E, Dudaladava V, Winiarski B, Scieglińska D, Widlak P (2007) Heat shock transcription factor 1 down-regulates spermatocyte-specific 70 kDa heat shock protein expression prior to the induction of apoptosis in mouse testes. Genes Cells 12:487–499

    PubMed  CAS  Google Scholar 

  119. Nakai A, Suzuki M, Tanabe M (2000) Arrest of spermatogenesis in mice expressing an active heat shock transcription factor 1. EMBO J 19:1545–1554

    PubMed  CAS  Google Scholar 

  120. Izu H, Inouye S, Fujimoto M, Shiraishi K, Naito K, Nakai A (2004) Heat shock transcription factor 1 is involved in quality-control mechanisms in male germ cells. Biol Reprod 70:18–24

    PubMed  CAS  Google Scholar 

  121. Vydra N, Malusecka E, Jarzab M, Lisowska K, Glowala-Kosinska M, Benedyk K, Widlak P, Krawczyk Z, Widlak W (2006) Spermatocyte-specific expression of constitutively active heat shock factor 1 induces HSP70i-resistant apoptosis in male germ cells. Cell Death Differ 13:212–222

    PubMed  CAS  Google Scholar 

  122. Widlak W, Winiarski B, Krawczyk A, Vydra N, Malusecka E, Krawczyk Z (2007) Inducible 70 kDa heat shock protein does not protect spermatogenic cells from damage induced by cryptorchidism. Int J Androl 30:80–87

    PubMed  CAS  Google Scholar 

  123. Le Masson F, Razak Z, Kaigo M, Audouard C, Charry C, Cooke H, Westwood JT, Christians ES (2011) Identification of heat shock factor 1 molecular and cellular targets during embryonic and adult female meiosis. Mol Cell Biol 31:3410–3423

    PubMed  Google Scholar 

  124. Zhang K, Shang Y, Liao S, Zhang W, Nian H, Liu Y, Chen Q, Han C (2007) Uncoupling protein 2 protects testicular germ cells from hyperthermia-induced apoptosis. Biochem Biophys Res Commun 360:327–332

    PubMed  CAS  Google Scholar 

  125. Kubota H, Sasaki S, Kubota Y, Umemoto Y, Yanai Y, Tozawa K, Hayashi Y, Kohri K (2011) Cyclooxygenase-2 protects germ cells against spermatogenesis disturbance in experimental cryptorchidism model mice. J Androl 32:77–85

    PubMed  CAS  Google Scholar 

  126. Fujisawa M, Matsumoto O, Kamidono S, Hirose F, Kojima K, Yoshida S (1988) Changes of enzymes involved in DNA synthesis in the testes of cryptorchid rats. J Reprod Fertil 84:123–130

    PubMed  CAS  Google Scholar 

  127. Kong WH, Zheng G, LU JN, Tso JK (2000) Temperature dependent expression of cdc2 and cyclin B1 in spermatogenic cells during spermatogenesis. Cell Res 10:289–302

    PubMed  CAS  Google Scholar 

  128. Tramontano F, Malanga M, Farina B, Jones R, Quesada P (2000) Heat stress reduces poly(ADPR)polymerase expression in rat testis. Mol Hum Reprod 6:575–581

    PubMed  CAS  Google Scholar 

  129. Zhang Y, Yang X, Cao H, Chen Z, Du Y, Kong W (2008) Heat stress induces Cdc2 protein decrease prior to mouse spermatogenic cell apoptosis. Acta Histochem 110:276–284

    PubMed  CAS  Google Scholar 

  130. Holcik M, Sonenberg N (2005) Translational control in stress and apoptosis. Nat Rev Mol Cell Biol 6:318–327

    PubMed  CAS  Google Scholar 

  131. Nakamura M, Hall PF (1978) The influence of temperature upon polysomes of spermatids of rat testes. Biochem Biophys Res Commun 85:756–761

    PubMed  CAS  Google Scholar 

  132. Nakamura M, Romrell LJ, Hall PF (1978) The effects of temperature and glucose on protein biosynthesis by immature (round) spermatids from rat testes. J Cell Biol 79:1–9

    PubMed  CAS  Google Scholar 

  133. Cataldo L, Mastrangelo MA, Kleene KC (1997) 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 231:206–213

    PubMed  CAS  Google Scholar 

  134. Nakamura M, Hall PF (1980) The mechanism by which body temperature inhibits protein biosynthesis in spermatids of rat testes. J Biol Chem 255:2907–2913

    PubMed  CAS  Google Scholar 

  135. Rowlands AG, Panniers R, Henshaw EC (1988) The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2. J Biol Chem 263:5526–5533

    PubMed  CAS  Google Scholar 

  136. Krishnamoorthy T, Pavitt GD, Zhang F, Dever TE, Hinnebusch AG (2001) Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation. Mol Cell Biol 21:5018–5030

    PubMed  CAS  Google Scholar 

  137. Dever TE (2002) Gene-specific regulation by general translation factors. Cell 108:545–556

    PubMed  CAS  Google Scholar 

  138. Dever TE, Feng L, Wek RC, Cigan AM, Donahue TF, Hinnebusch AG (1992) Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Cell 68:585–596

    PubMed  CAS  Google Scholar 

  139. Lu PD, Harding HP, Ron D (2004) Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. J Cell Biol 167:27–33

    PubMed  CAS  Google Scholar 

  140. Jiang HY, Wek RC (2005) Phosphorylation of the alpha-subunit of the eukaryotic initiation factor-2 (eIF2alpha) reduces protein synthesis and enhances apoptosis in response to proteasome inhibition. J Biol Chem 280:14189–14202

    PubMed  CAS  Google Scholar 

  141. Bevilacqua E, Wang X, Majumder M, Gaccioli F, Yuan CL, Wang C, Zhu X, Jordan LE, Scheuner D, Kaufman RJ, Koromilas AE, Snider MD, Holcik M, Hatzoglou M (2010) eIF2alpha phosphorylation tips the balance to apoptosis during osmotic stress. J Biol Chem 285:17098–17111

    PubMed  CAS  Google Scholar 

  142. Sarge KD, Bray AE, Goodson ML (1995) Altered stress response in testis. Nature 374:126

    PubMed  CAS  Google Scholar 

  143. Anckar J, Sistonen L (2011) Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem 80:1089–1115

    PubMed  CAS  Google Scholar 

  144. Han AP, Yu C, Lu L, Fujiwara Y, Browne C, Chin G, Fleming M, Leboulch P, Orkin SH, Chen JJ (2001) Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. EMBO J 20:6909–6918

    PubMed  CAS  Google Scholar 

  145. Lu L, Han AP, Chen JJ (2001) Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses. Mol Cell Biol 21:7971–7980

    PubMed  CAS  Google Scholar 

  146. Barber GN (2005) The dsRNA-dependent protein kinase, PKR and cell death. Cell Death Differ 12:563–570

    PubMed  CAS  Google Scholar 

  147. Patil C, Walter P (2001) Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr Opin Cell Biol 13:349–355

    PubMed  CAS  Google Scholar 

  148. Kimball SR (2001) Regulation of translation initiation by amino acids in eukaryotic cells. Prog Mol Subcell Biol 26:155–184

    PubMed  CAS  Google Scholar 

  149. Deng J, Harding HP, Raught B, Gingras AC, Berlanga JJ, Scheuner D, Kaufman RJ, Ron D, Sonenberg N (2002) Activation of GCN2 in UV-irradiated cells inhibits translation. Curr Biol 12:1279–1286

    PubMed  CAS  Google Scholar 

  150. Zhan K, Vattem KM, Bauer BN, Dever TE, Chen JJ, Wek RC (2002) Phosphorylation of eukaryotic initiation factor 2 by heme-regulated inhibitor kinase-related protein kinases in Schizosaccharomyces pombe is important for resistance to environmental stresses. Mol Cell Biol 22:7134–7146

    PubMed  CAS  Google Scholar 

  151. Anderson P, Kedersha N (2002) Stressful initiations. J Cell Sci 115:3227–3234

    PubMed  CAS  Google Scholar 

  152. Kedersha NL, Gupta M, Li W, Miller I, Anderson P (1999) RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J Cell Biol 147:1431–1442

    PubMed  CAS  Google Scholar 

  153. Kedersha N, Chen S, Gilks N, Li W, Miller IJ, Stahl J, Anderson P (2002) Evidence that ternary complex (eIF2-GTP-tRNA Meti )-deficient preinitiation complexes are core constituents of mammalian stress granules. Mol Biol Cell 13:195–210

    PubMed  CAS  Google Scholar 

  154. Buchan JR, Parker R (2009) Eukaryotic stress granules: the ins and outs of translation. Mol Cell 36:932–941

    PubMed  CAS  Google Scholar 

  155. Kedersha N, Cho MR, Li W, Yacono PW, Chen S, Gilks N, Golan DE, Anderson P (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J Cell Biol 151:1257–1268

    PubMed  CAS  Google Scholar 

  156. Kedersha N, Stoecklin G, Ayodele M, Yacono P, Lykke-Andersen J, Fritzler MJ, Scheuner D, Kaufman RJ, Golan DE, Anderson P (2005) Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol 169:871–884

    PubMed  CAS  Google Scholar 

  157. Kim WJ, Back SH, Kim V, Ryu I, Jang SK (2005) Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions. Mol Cell Biol 25:2450–2462

    PubMed  CAS  Google Scholar 

  158. Arimoto K, Fukuda H, Imajoh-Ohmi S, Saito H, Takekawa M (2008) Formation of stress granules inhibits apoptosis by suppressing stress-responsive MAPK pathways. Nat Cell Biol 10:1324–1332

    PubMed  CAS  Google Scholar 

  159. Ohn T, Kedersha N, Hickman T, Tisdale S, Anderson P (2008) A functional RNAi screen links O-GlcNAc modification of ribosomal proteins to stress granule and processing body assembly. Nat Cell Biol 10:1224–1231

    PubMed  CAS  Google Scholar 

  160. Saxena R, de Vries JW, Repping S, Alagappan RK, Skaletsky H, Brown LG, Ma P, Chen E, Hoovers JM, Page DC (2000) Four DAZ genes in two clusters found in the AZFc region of the human Y chromosome. Genomics 67:256–267

    PubMed  CAS  Google Scholar 

  161. Kim B, Lee Y, Kim Y, Lee KH, Chun S, Rhee K, Seo JT, Kim SW, Paick JS (2009) Polymorphic expression of DAZ proteins in the human testis. Hum Reprod 24:1507–1515

    PubMed  CAS  Google Scholar 

  162. Yen PH, Chai NN, Salido EC (1996) The human autosomal gene DAZLA: testis specificity and a candidate for male infertility. Hum Mol Genet 5:2013–2017

    PubMed  CAS  Google Scholar 

  163. Xu EY, Moore FL, Pera RA (2001) A gene family required for human germ cell development evolved from an ancient meiotic gene conserved in metazoans. Proc Natl Acad Sci USA 98:7414–7419

    PubMed  CAS  Google Scholar 

  164. Eberhart CG, Maines JZ, Wasserman SA (1996) Meiotic cell cycle requirement for a fly homologue of human Deleted in Azoospermia. Nature 381:783–785

    PubMed  CAS  Google Scholar 

  165. Ruggiu M, Speed R, Taggart M, KcKay SJ, Kilanowski F, Saunders P, Dorin J, Cooke HJ (1997) The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389:73–77

    PubMed  CAS  Google Scholar 

  166. Houston DW, King ML (2000) A critical role for Xdazl, a germ plasm-localized RNA, in the differentiation of primordial germ cells in Xenopus. Development 127:447–456

    PubMed  CAS  Google Scholar 

  167. Karashima T, Sugimoto A, Yamamoto M (2000) Caenorhabditis elegans homologue of the human azoospermia factor DAZ is required for oogenesis but not for spermatogenesis. Development 127:1069–1079

    PubMed  CAS  Google Scholar 

  168. Shah C, Vangompel MJ, Naeem V, Chen Y, Lee T, Angeloni N, Wang Y, Xu EY (2010) Widespread presence of human BOULE homologs among animals and conservation of their ancient reproductive function. PLoS Genet 6:e1001022

    PubMed  Google Scholar 

  169. Lin Y, Gill ME, Koubova J, Page DC (2008) Germ cell-intrinsic and -extrinsic factors govern meiotic initiation in mouse embryos. Science 322:1685–1687

    PubMed  CAS  Google Scholar 

  170. Kee K, Angeles VT, Flores M, Nguyen HN, Reijo Pera RA (2009) Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature 462:222–225

    PubMed  CAS  Google Scholar 

  171. Chen J, Melton C, Suh N, Oh JS, Horner K, Xie F, Sette C, Blelloch R, Conti M (2011) Genome-wide analysis of translation reveals a critical role for deleted in azoospermia-like (Dazl) at the oocyte-to-zygote transition. Genes Dev 25:755–766

    PubMed  CAS  Google Scholar 

  172. Collier B, Gorgoni B, Loveridge C, Cooke HJ, Gray NK (2005) The DAZL family proteins are PABP-binding proteins that regulate translation in germ cells. EMBO J 24:2656–2666

    PubMed  CAS  Google Scholar 

  173. Reynolds N, Collier B, Maratou K, Bingham V, Speed RM, Taggart M, Semple CA, Gray NK, Cooke HJ (2005) Dazl binds in vivo to specific transcripts and can regulate the pre-meiotic translation of Mvh in germ cells. Hum Mol Genet 14:3899–3909

    PubMed  CAS  Google Scholar 

  174. Reynolds N, Collier B, Bingham V, Gray NK, Cooke HJ (2007) Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl. RNA 13:974–981

    PubMed  CAS  Google Scholar 

  175. Lee KH, Lee S, Kim B, Chang S, Kim SW, Paick JS, Rhee K (2006) Dazl can bind to dynein motor complex and may play a role in transport of specific mRNAs. EMBO J 25:4263–4270

    PubMed  CAS  Google Scholar 

  176. VanGompel MJ, Xu EY (2010) A novel requirement in mammalian spermatid differentiation for the DAZ-family protein Boule. Hum Mol Genet 19:2360–2369

    PubMed  CAS  Google Scholar 

  177. Pothof J, Verkaik NS, van IJcken W, Wiemer EA, Ta VT, van der Horst GT, Jaspers NG, van Gent DC, Hoeijmakers JH, Persengiev SP (2009) MicroRNA-mediated gene silencing modulates the UV-induced DNA-damage response. EMBO J 28:2090–2099

    PubMed  CAS  Google Scholar 

  178. Kon Y, Endoh D (2001) Heat-shock resistance in experimental cryptorchid testis of mice. Mol Reprod Dev 58:216–222

    PubMed  CAS  Google Scholar 

  179. Allen RL, O’Brien DA, Jones CC, Rockett DL, Eddy EM (1988) Expression of heat shock proteins by isolated mouse spermatogenic cells. Mol Cell Biol 8:3260–3266

    PubMed  CAS  Google Scholar 

  180. Nishiyama H, Danno S, Kaneko Y, Itoh K, Yokoi H, Fukumoto M, Okuno H, Millán JL, Matsuda T, Yoshida O, Fujita J (1998) Decreased expression of cold-inducible RNA-binding protein (CIRP) in male germ cells at elevated temperature. Am J Pathol 152:289–296

    PubMed  CAS  Google Scholar 

  181. Iuchi Y, Kaneko T, Matsuki S, Sasagawa I, Fujii J (2003) Concerted changes in the YB2/RYB-a protein and protamine 2 messenger RNA in the mouse testis under heat stress. Biol Reprod 68:129–135

    PubMed  CAS  Google Scholar 

  182. Li W, Bao W, Ma J, Liu X, Xu R, Wang RA, Zhang Y (2008) Metastasis tumor antigen 1 is involved in the resistance to heat stress-induced testicular apoptosis. FEBS Lett 582:869–873

    PubMed  CAS  Google Scholar 

  183. Farooqui SM, Al-Bagdadi F, Houslay MD, Bolger GB, Stout R, Specian RD, Cherry JA, Conti M, O’Donnell JM (2001) Surgically induced cryptorchidism-related degenerative changes in spermatogonia are associated with loss of cyclic adenosine monophosphate-dependent phosphodiesterases type 4 in abdominal testes of rats. Biol Reprod 64:1583–1589

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Howard J. Cooke and our lab members, especially Won Yul Jang and Miseon Lee, for critical reading of the manuscript. This study was supported by grants from the BioImaging Research Center at GIST; the Basic Research Program [grant number 3344-20100052]; the Science Research Center Program [grant number R11-2005-009-030050] of the Ministry of Education, Science and Technology; and the second stage of the Brain Korea 21 Project in 2009 (to B.K.) and 2011 (to K.P.).

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  1. Department of Biological Sciences, Seoul National University, Seoul, 151-747, Korea

    Byunghyuk Kim, Kyosun Park & Kunsoo Rhee

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Kim, B., Park, K. & Rhee, K. Heat stress response of male germ cells. Cell. Mol. Life Sci. 70, 2623–2636 (2013). https://doi.org/10.1007/s00018-012-1165-4

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