Andrologie

, Volume 15, Issue 3, pp 263–277 | Cite as

Mort programmée des cellules germinales testiculaires: causes et mécanismes mis en jeu

  • Souheila Amara
  • Aline Bozec
  • Mohamed Benahmed
  • Claire Mauduit
Revue Apoptose

Résumé

La spermatogenèse résulte d'un équilibre entre prolifération et apoptose. Si cet équilibre est rompu il peut conduire à certaines pathologies testiculaires: cancers testiculaires, infertilités. L'apoptose semble être particulièrement importante lors de la spermatogenèse puisque 60 à 75% des cellules germinales formées n'atteignent pas le stade spermatozoïde.

Dans les cellules germinales de rongeurs ou bien humaines, les différentes molécules de l'apoptose ont été détectées: caspases effectrices qui sont au cœur du processus et en amont les protéines de la voie des récepteurs de mort ou de la voie mitochondriale. Selon le type d'apoptose des cellules germinales (apoptose physiologique, induite par un retrait hormonal, par des lésions chimiques ou physiques), une ou les différentes voies entrent en jeu.

Enfin, dans différentes pathologies testiculaires humaines, les voies de l'apoptose et particulièrement les caspases semblent être impliquées.

Mots clés

spermatogenèse apoptose caspases Bcl2 récepteurs de mort infertilité masculine 

Apoptotic process in testicular germ cells: causes and mechanisms

Abstract

Spermatogenesis results from a balance between proliferation and apoptosis. An alteration in this balance could lead to testicular diseases such as testicular tumour or infertility. Apoptosis seem to be important in regulating the processes of spermatogenesis since 60 to 75% of germ cells do not reach the spermatozoa stage. The various molecules of the apoptotic cascade have been detected in rodent or human germ cells, such as effector caspases and upstream proteins from cell death receptor or mitochondrial pathways. One or several different pathways may be involved in the germ cell apoptotic process triggered physiologically, by hormonal deprivation, or by chemical or physical inducers. Finally, caspases appear to play a role in various testicular diseases (particularly infertility).

Key words

spermatogenesis apoptosis caspases Bcl2 death receptor pathways male infertility 

References

  1. 1.
    ADAMS J.M., CORY S.: The Bcl-2 protein family: arbiters of cell survival. Science, 1998, 281: 1322–1326.PubMedCrossRefGoogle Scholar
  2. 2.
    ALLAN D.J., HARMON B.V., ROBERTS S.A.: Spermatogonial apoptosis has three morphologically recognizable phases and shows no circadian rhythm during normal spermatogenesis in the rat. Cell Prolif., 1992, 25: 241–250.PubMedCrossRefGoogle Scholar
  3. 3.
    ANTICH M., FABIAN E., SARQUELLA J. et al.: Effect of testicular damage induced by cryptorchidism on insulin-like growth factor I receptors in rat Sertoli cells. J. Reprod. Fertil., 1995, 104: 267–275.PubMedGoogle Scholar
  4. 4.
    BARQAWI A., CARUSO A., MEACHAM R.B.: Experimental varicocele induces testicular germ cell apoptosis in the rat. J. Urol., 2004, 171: 501–503.PubMedCrossRefGoogle Scholar
  5. 5.
    BARQAWI A., TRUMMER H., MEACHAM R.: Effect of prolonged cryptorchidism on germ cell apoptosis and testicular sperm count. Asian J. Androl., 2004, 6: 47–51.PubMedGoogle Scholar
  6. 6.
    BARTKE A.: Apoptosis of male germ cells, a generalized or a cell type-specific phenomenon? Endocrinology, 1995, 136: 3–4.PubMedCrossRefGoogle Scholar
  7. 7.
    BEUMER T.L., ROEPERS-GAJADIEN H.L., GADEMAN I.S. et al.: The role of the tumor suppressor p53 in spermatogenesis. Cell Death Differ., 1998, 5: 669–677.PubMedCrossRefGoogle Scholar
  8. 8.
    BILLIG H., FURUTA I., RIVIER C. et al.: Apoptosis in testis germ cells: developmental changes in gonadotropin dependence and localization to selective tubule stages. Endocrinology, 1995, 136: 5–12.PubMedCrossRefGoogle Scholar
  9. 9.
    BLANCO-RODRIGUEZ J., MARTINEZ-GARCIA C.: Apoptosis is physiologically restricted to a specialized cytoplasmic compartment in rat spermatids. Biol. Reprod., 1999, 61: 1541–1547.PubMedCrossRefGoogle Scholar
  10. 10.
    BOEKELHEIDE K., FLEMING S.L., JOHNSON K.J. et al.: Role of Sertoli cells in injury-associated testicular germ cell apoptosis. Proc. Soc. Exp. Biol. Med., 2000, 225: 105–115.PubMedCrossRefGoogle Scholar
  11. 11.
    BOZEC A., CHUZEL F., CHATER S. et al.: The mitochondrial-dependent pathway is chronically affected in testicular germ cell death in adult rats exposed in utero to anti-androgens. J. Endocrinol., 2004, 183: 79–90.PubMedCrossRefGoogle Scholar
  12. 12.
    BUDNIK L.T., JAHNER D., MUKHOPADHYAY A.K.: Inhibitory effects of TNF alpha on mouse tumor Leydig cells: possible role of ceramide in the mechanism of action. Mol. Cell. Endocrinol., 1999, 150: 39–46.PubMedCrossRefGoogle Scholar
  13. 13.
    BUJAN L., MIEUSSET R.: Contraception masculine par la chaleur. Contracept. Fertil. Sex., 1995, 23: 611–614.PubMedGoogle Scholar
  14. 14.
    CHAUDHARY P.M., EBY M., JASMIN A. et al.: Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity, 1997, 7: 821–830.PubMedCrossRefGoogle Scholar
  15. 15.
    CONWAY E.M., POLLEFEYT S., CORNELISSEN J. et al.: Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions. Blood, 2000, 95: 1435–1442.PubMedGoogle Scholar
  16. 16.
    CORDELLI E., FRESEGNA A.M., LETER G. et al.: Evaluation of DNA damage in different stages of mouse spermatogenesis after testicular X irradiation. Radiat. Res., 2003, 160: 443–451.PubMedCrossRefGoogle Scholar
  17. 17.
    CROMTON M.: Bax, Bid and the permeabilization of the mitochondrial outer membrane in apoptosis. Curr. Opin. Cell. Biol., 2000, 12: 414–419.CrossRefGoogle Scholar
  18. 18.
    DATTA R., OKI E., ENDO K. et al.: XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage. J. Biol. Chem., 2000, 275: 31733–31738.PubMedCrossRefGoogle Scholar
  19. 19.
    DE FRANCA L.R., GHOSH S., YE S.J. et al.: Surface and surface-to-volume relationships of the Sertoli cell during the cycle of the seminiferous epithelium in the rat. Biol. Reprod., 1993, 49: 1215–1228.PubMedCrossRefGoogle Scholar
  20. 20.
    DE S.K., CHEN H.L., PACE J.L. et al.: Expression of tumor necrosis factor-alpha in mouse spermatogenic cells. Endocrinology, 1993, 133: 389–396.PubMedCrossRefGoogle Scholar
  21. 21.
    DEVERAUX Q.L., REED J.C.: IAP family proteins—suppressors of apoptosis. Genes Dev., 1999, 13: 239–252.PubMedCrossRefGoogle Scholar
  22. 22.
    DIERICH A., SAIRAM M.R., MONACO L. et al.: Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc. Natl Acad. Sci. USA, 1998, 95: 13612–136177.PubMedCrossRefGoogle Scholar
  23. 23.
    DUNDAR M., KOCAK I., CULHACI N.: A new experimental model for cryptorchidism: inguinoscrotal approach. Urol. Res., 2001, 29: 178–181.PubMedCrossRefGoogle Scholar
  24. 24.
    EVAN G., LITTLEWOOD T.: A matter of life and cell death. Science, 1998, 281: 1317–1322.PubMedCrossRefGoogle Scholar
  25. 25.
    FAROOQUI S.M., AL-BAGDADI F., HOUSLAY M.D. et al.: 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., 2001, 64: 1583–1589.PubMedCrossRefGoogle Scholar
  26. 26.
    FELDAMN M., TAYLOR P., PALEOLOG E. et al.: Anti-TNF alpha therapy is useful in rheumatoid arthritis and Crohn's disease: analysis of the mechanism of action predicts utility in other diseases. Transplant Proc., 1998, 30: 4126–4127.CrossRefGoogle Scholar
  27. 27.
    FISHER J.S.: Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. Reproduction, 2004, 127: 305–315.PubMedCrossRefGoogle Scholar
  28. 28.
    FRANCAVILLA S., D'ABRIZIO P., RUCCI N. et al.: Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis. J. Clin. Endocrinol. Metab., 2000, 85: 2692–2700.PubMedCrossRefGoogle Scholar
  29. 29.
    FUJISAWA M., HIRAMINE C., TANAKA H. et al.: Decrease in apoptosis of germ cells in the testes of infertile men with varicocele. World J. Urol., 1999, 17: 296–300.PubMedCrossRefGoogle Scholar
  30. 30.
    FURUCHI T., MASUKO K., NISHIMUNE Y. et al.: Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spermatogonia. Development, 1996, 122: 1703–1709.PubMedGoogle Scholar
  31. 31.
    GANDINI L., LOMBARDO F., PAOLI D. et al.: Study of apoptotic DNA fragmentation in human spermatozoa. Hum. Reprod., 2000, 15: 830–839.PubMedCrossRefGoogle Scholar
  32. 32.
    GODDARD I., FLORIN A., MAUDUIT C. et al.: Alteration of lactate production and transport in the adult rat testis exposed in utero to flutamide. Mol. Cell. Endocrinol., 2003, 206: 137–146.PubMedCrossRefGoogle Scholar
  33. 33.
    GRATAROLI R., VINDRIEUX D., GOUGEON A. et al.: Expression of tumor necrosis factor-alpha-related apoptosis-inducing ligand and its receptors in rat testis during development. Biol. Reprod., 2002, 66: 1707–1715.PubMedCrossRefGoogle Scholar
  34. 34.
    GRAY L.E. Jr., OSTBY J., FURR J. et al.: Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol. Sci., 2000, 58: 350–365.PubMedCrossRefGoogle Scholar
  35. 35.
    GRAY L.E. Jr., OSTBY J.S., KELCE W.R.: Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat. Toxicol. Appl. Pharmacol., 1994, 129: 46–52.PubMedCrossRefGoogle Scholar
  36. 36.
    GRAY L.E. Jr., WOLF C., LAMBRIGHT C. et al.: Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p′-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol. Ind. Health, 1999, 15: 94–118.PubMedCrossRefGoogle Scholar
  37. 37.
    GUPTA S., RADHA V., FURUKAWA Y. et al.: Direct transcriptional activation of human caspase-1 by tumor suppressor p53. J. Biol. Chem., 2001, 276: 10585–10588.PubMedCrossRefGoogle Scholar
  38. 38.
    HANEJI T., MAEKAWA M., NISHIMUNE Y.: Vitamin A and follicle-stimulating hormone synergistically induce differentiation of type A spermatogonia in adult mouse cryptorchid testes in vitro. Endocrinology, 1984, 114: 801–805.PubMedGoogle Scholar
  39. 39.
    HENRIKSEN K., HAKOVIRTA H., PARVINEN M.: Testosterone inhibits and induces apoptosis in rat seminiferous tubules in a stage-specific manner: in situ quantification in squash preparations after administration of ethane dimethane sulfonate. Endocrinology, 1995, 136: 3285–3291.PubMedCrossRefGoogle Scholar
  40. 40.
    HIKIM A.P., LUE Y., YAMAMOTO C.M. et al.: Key apoptotic pathways for heat-induced programmed germ cell death in the testis. Endocrinology, 2003, 144: 3167–3175.PubMedCrossRefGoogle Scholar
  41. 41.
    HOCKENBERY D.M., ZUTTER M., HICKEY W. et al.: BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc. Natl Acad. Sci. USA, 1991, 88: 6961–6965.PubMedCrossRefGoogle Scholar
  42. 42.
    HUCKINS C.: The morphology and kinetics of spermatogonial degeneration in normal adult rats: an analysis using a simplified classification of the germinal epithelium. Anat. Rec., 1978, 190: 905–926.PubMedCrossRefGoogle Scholar
  43. 43.
    HULEIHEL M., LUNENFELD E.: Regulation of spermatogenesis by paracrine/autocrine testicular factors. Asian J. Androl., 2004, 6: 259–268.PubMedGoogle Scholar
  44. 44.
    IMPERATO-McGINLEY J., SANCHEZ R.S., SPENCER J.R. et al.: Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies. Endocrinology, 1992, 131: 1149–1156.PubMedCrossRefGoogle Scholar
  45. 45.
    ITO K., TANEMURA K., GOTOH H. et al.: Apoptosis-like cell death in experimentally-induced cryptorchidism in adult mice. J. Vet. Med. Sci., 1997, 59: 353–359.PubMedCrossRefGoogle Scholar
  46. 46.
    JEYAKUMAR M., SURESH R., KRISHNAMURTHY H.N. et al.: Changes in testicular function following specific deprivation of LH in the adult male rabbit. J. Endocrinol., 1995, 147: 111–120.PubMedCrossRefGoogle Scholar
  47. 47.
    JOSHI D.S., YICK J., MURRAY D. et al.: Stage-dependent variation in the radiosensitivity of DNA in developing male germ cells. Radiat. Res., 1990, 121: 274–281.PubMedCrossRefGoogle Scholar
  48. 48.
    KASOF G.M., GOMES B.C.: Livin, a novel inhibitor of apoptosis protein family member. J. Biol. Chem., 2001, 276: 3238–3246.PubMedCrossRefGoogle Scholar
  49. 49.
    KAYAGAKI N., KAWASAKI A., EBATA T. et al.: Metalloproteinase-mediated release of human Fas ligand. J. Exp. Med., 1995, 182: 1777–1783.PubMedCrossRefGoogle Scholar
  50. 50.
    KEENEY D.S., MENDIS-HANDAGAMA S.M., ZiRKIN B.R. et al.: Effect of long term deprivation of luteinizing hormone on Leydig cell volume, Leydig cell number, and steroidogenic capacity of the rat testis. Endocrinology, 1988, 123: 2906–2915.PubMedGoogle Scholar
  51. 51.
    KEENEY D.S., SPRANDO R.L., ROBAIRE B. et al.: Reversal of long-term LH deprivation on testosterone secretion and Leydig cell volume, number and proliferation in adult rats. J. Endocrinol., 1990, 127: 47–58.PubMedCrossRefGoogle Scholar
  52. 52.
    KERR J.F., WYLLIE A.H., CURRIE A.R.: Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer, 1972, 26: 239–257.PubMedGoogle Scholar
  53. 53.
    KILINC F., GUVEL S., KAYASELCUK F. et al.: p53 Expression and apoptosis in varicocele int the rat testis. J. Urol., 2004, 172: 2475–2478.PubMedCrossRefGoogle Scholar
  54. 54.
    KIM J.M., GHOSH S.R., WEIL A.C. et al.: Caspase-3 and caspase-activated deoxyribonuclease are associated with testicular germ cell apoptosis resulting from reduced intratesticular testosterone. Endocrinology, 2001, 142: 3809–3816.PubMedCrossRefGoogle Scholar
  55. 55.
    KITAYAMA T.: [Study on testicular temperature in men]. Hinyokika Kiyo, 1965, 11: 435–465.PubMedGoogle Scholar
  56. 56.
    KNUDSON C.M., TUNG K.S., TOURTELLOTTE W.G. et al.: Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science, 1995, 270: 96–99.PubMedCrossRefGoogle Scholar
  57. 57.
    KOCAK I., DUNDAR M., HEKIMGIL M. et al.: Assessment of germ cell apoptosis in cryptorchid rats. Asian J. Androl., 2002, 4: 183–186.PubMedGoogle Scholar
  58. 58.
    KOJIMA S., HATANO M., OKADA S. et al.: Testicular germ cell apoptosis in Bcl6-deficient mice. Development, 2001, 128: 57–65.PubMedGoogle Scholar
  59. 59.
    KRAJEWSKI S., BODRUG S., KRAJEWSKA M. et al.: Immunohistochemical analysis of Mcl-1 protein in human tissues. Differential regulation of Mcl-1 and Bcl-2 protein production suggests a unique role for Mcl-1 in control of programmed cell death in vivo. Am. J. Pathol., 1995, 146: 1309–1319.PubMedGoogle Scholar
  60. 60.
    KRISHNAMURTHY P.K., MAYS J.L., BIJUR G.N. et al.: Transient oxidative stress in SH-SY5Y human neuroblastoma cells results in caspase dependent and independent cell death and tau proteolysis. J. Neurosci. Res., 2000, 61: 515–523.PubMedCrossRefGoogle Scholar
  61. 61.
    LEE J., RICHBURG J.H., SHIPP E.B. et al.: The Fas system, a regulator of testicular germ cell apoptosis, is differentially upregulated in Sertoli cell versus germ cell injury of the testis. Endocrinology, 1999, 140: 852–858.PubMedCrossRefGoogle Scholar
  62. 62.
    LEE J., RICHBURG J.H., YOUNKIN S.C. et al.: The Fas system is a key regulator of germ cell apoptosis in the testis. Endocrinology, 1997, 138: 2081–2088.PubMedCrossRefGoogle Scholar
  63. 63.
    LIU Z.M., ZHENG X.M., LI S.W. et al.: Germ cell apoptosis and expression of Bcl-2 and Bax following testicular torsion/detorsion in rats. Zhonghua Nan Ke Xue, 2003, 9: 40–42.PubMedGoogle Scholar
  64. 64.
    LIU Z.P., LI W.Y., LIN B. et al.: Influence of FasL overexpression in transgenic mice on the immune regulative function of Sertoli cell. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2004, 20: 456–460.PubMedGoogle Scholar
  65. 65.
    LUE Y.H., HIKIM A.P., SWERDLOFF R.S. et al.: Single exposure to heat induces stage-specific germ cell apoptosis in rats: role of intratesticular testosterone on stage specificity. Endocrinology, 1999, 140: 1709–1717.PubMedCrossRefGoogle Scholar
  66. 66.
    LUE Y.H., LASLEY B.L., LAUGHLIN L.S. et al.: Mild testicular hyperthermia induces profound transitional spermatogenic suppression through increased germ cell apoptosis in adult cynomolgus monkeys (Macaca fascicularis). J. Androl., 2002, 23: 799–805.PubMedGoogle Scholar
  67. 67.
    MAUDUIT C., BESSET V., CAUSSANEL V. et al.: Tumor necrosis factor alpha receptor p55 is under hormonal (folliclestimulating hormone) control in testicular Sertoli cells. Biochem. Biophys. Res. Commun., 1996, 224: 631–637.PubMedCrossRefGoogle Scholar
  68. 68.
    MAUDUIT C., HARTMANN D.J., CHAUVIN M.A. et al.: Tumor necrosis factor alpha inhibits gonadotropin action in cultured porcine Leydig cells: site(s) of action. Endocrinology, 1991, 129: 2933–2940.PubMedCrossRefGoogle Scholar
  69. 69.
    MIEUSSET R., BUJAN L.: Testicular heating and its possible contributions to male infertility: a review. Int. J. Androl., 1995, 18: 169–184.PubMedCrossRefGoogle Scholar
  70. 70.
    MIGNON A., GUIDOTTI J.E., MITCHELL C. et al.: Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes. Nat. Med., 1998, 4: 1185–1188.PubMedCrossRefGoogle Scholar
  71. 71.
    MOORE C., HUTSON J.C.: Physiological relevance of tumor necrosis factor in mediating macrophage-Leydig cell interactions. Endocrinology, 1994, 134: 63–69.PubMedCrossRefGoogle Scholar
  72. 72.
    MORENO S.G., DUTRILLAUX B., COFFIGNY H.: Status of p53, p21, mdm2, pRb proteins, and DNA methylation in gonocytes of control and gamma-irradiated rats during testicular development. Biol. Reprod., 2001, 64: 1422–1431.PubMedCrossRefGoogle Scholar
  73. 73.
    MYLCHREEST E., CATTLEY R.C., FOSTER P.M.: Male reproductive tract malformations in rats following gestational and lactational exposure to Di(n-butyl) phthalate: an antiandrogenic mechanism? Toxicol. Sci., 1998, 43: 47–60.PubMedGoogle Scholar
  74. 74.
    NAGATA S., GOLSTEIN P.: The Fas death factor. Science, 1995, 267: 1449–1456.PubMedCrossRefGoogle Scholar
  75. 75.
    NANDI S., BANERJEE P.P., ZIRKIN B.R.: Germ cell apoptosis in the testes of Sprague Dawley rats following testosterone withdrawal by ethane 1,2-dimethanesulfonate administration: relationship to Fas? Biol. Reprod., 1999, 61: 70–75.PubMedCrossRefGoogle Scholar
  76. 76.
    OGI S., TANJI N., YOKOYAMA M. et al.: Involvement of Fas in the apoptosis of mouse germ cells induced by experimental cryptorchidism. Urol. Res., 1998, 26: 17–21.PubMedCrossRefGoogle Scholar
  77. 77.
    OLDEREID N.B., ANGELIS P.D., WIGER R. et al.: Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis. Mol. Hum. Reprod., 2001, 7: 403–408.PubMedCrossRefGoogle Scholar
  78. 78.
    OMEZZINE A., CHATER S., MAUDUIT C. et al.: Long-term apoptotic cell death process with increased expression and activation of caspase-3 and-6 in adult rat germ cells exposed in utero to flutamide. Endocrinology, 2003, 144: 648–661.PubMedCrossRefGoogle Scholar
  79. 79.
    ORTH J.M.: Cell Biology of testicular development in fetus and neonate. In: Desjardins C., Ewing L.L. eds. Cell and molecular biology of testis. New York, Oxford University Press, 1993: 3–4.Google Scholar
  80. 80.
    PAREDES ESTEBAN R.M., RAMIREZ CHAMOND R., CARRACEDE ANON J. et al.: [Valoration of the FAS in the contralateral testis after unilateral testicular torsion. Experimental study in rats]. Cir. Pediatr., 2003, 16: 4–7.PubMedGoogle Scholar
  81. 81.
    PENTIKAINEN V., ERKKILA K., DUNKEL L.: Fas regulates germ cell apoptosis in the human testis in vitro. Am. J. Physiol., 1999, 276: E310-E316.PubMedGoogle Scholar
  82. 82.
    PENTIKAINEN V., SUOMALAINEN L., ERKKILA K. et al.: Nuclear factor-kappa B activation in human testicular apoptosis. Am. J. Pathol., 2002, 160: 205–218.PubMedGoogle Scholar
  83. 83.
    PEREZ G.I., ROBLES R., KNUDSON C.M. et al.: Prolongation of ovarian lifespan into advanced chronological age by Baxdeficiency. Nat. Genet., 1999, 21: 200–203.PubMedCrossRefGoogle Scholar
  84. 84.
    PETER A.T., LINDE-FORSBERG C.: Efficacy of the anticaspase agent zVAD-fmk on post-thaw viability of canine spermatozoa. Theriogenology, 2003, 59: 1525–1532.PubMedCrossRefGoogle Scholar
  85. 85.
    PRINT C.G., LOVELAND K.L.: Germ cell suicide: new insights into apoptosis during spermatogenesis. Bioessays, 2000, 22: 423–430.PubMedCrossRefGoogle Scholar
  86. 86.
    PRINT C.G., LOVELAND K.L., GIBSON L. et al.: Apoptosis regulator bcl-w is essential for spermatogenesis but appears otherwise redundant. Proc. Natl Acad. Sci. USA, 1998, 95: 12424–12431.PubMedCrossRefGoogle Scholar
  87. 87.
    RICHBURG J.H.: The relevance of spontaneous-and chemically-induced alterations in testicular germ cell apoptosis to toxicology. Toxicol. Lett., 2000, 112–113: 79–86.PubMedCrossRefGoogle Scholar
  88. 88.
    RICHTER B.W., MIR S.S., EIBEN L.J. et al.: Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family. Mol. Cell. Biol., 2001, 21: 4292–4301.PubMedCrossRefGoogle Scholar
  89. 89.
    RODRIGUEZ I., ODY C., ARAKI K. et al.: An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis. Embo. J., 1997, 16: 2262–2270.PubMedCrossRefGoogle Scholar
  90. 90.
    ROSSI P., DOLCI S., ALBANESI C. et al.: Follicle-stimulating hormone induction of steel factor (SLF) mRNA in mouse Sertoli cells and stimulation of DNA synthesis in spermatogonia by soluble SLF. Dev. Biol., 1993, 155: 68–74.PubMedCrossRefGoogle Scholar
  91. 91.
    ROY N., DEVERAUX Q.L., TAKAHASHI R. et al.: The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. Embo. J., 1997, 16: 6914–6925.PubMedCrossRefGoogle Scholar
  92. 92.
    RUCKER E.B. 3rd, DIERISSEAU P., WAGNER K.U. et al.: Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol. Endocrinol., 2000, 14: 1038–1052.PubMedCrossRefGoogle Scholar
  93. 93.
    RUSSELL L.D., CHIARINI-GARCIA H., KORSMEYER S.J. et al.: Bax-dependent spermatogonia apoptosis is required for testicular development and spermatogenesis. Biol. Reprod., 2002, 66: 950–958.PubMedCrossRefGoogle Scholar
  94. 94.
    SAID T.M., PAASCH U., GLANDER H.J. et al.: Role of caspases in male infertility. Hum. Reprod. Update, 2004, 10: 39–51.PubMedCrossRefGoogle Scholar
  95. 95.
    SAKKAS D., MOFFATT O., MANICARDI G.C. et al.: Nature of DNA damage in ejaculated human spermatozoa and the possible involvement of apoptosis. Biol. Reprod., 2002, 66: 1061–1067.PubMedCrossRefGoogle Scholar
  96. 96.
    SCHENDEL S.L., MONTAL M., REED J.C.: Bcl-2 family proteins as ion-channels. Cell. Death Differ., 1998, 5: 372–380.PubMedCrossRefGoogle Scholar
  97. 97.
    SHARPE R.M., KERR J.B., McKINNELL C. et al.: Temporal relationship between androgen-dependent changes in the volume of seminiferous tubule fluid, lumen size and seminiferous tubule protein secretion in rats. J. Reprod. Fertil., 1994, 101: 193–198.PubMedCrossRefGoogle Scholar
  98. 98.
    SHIKONE T., BILLIG H., HSUEH A.J.: Experimentally induced cryptorchidism increases apoptosis in rat testis. Biol. Reprod., 1994, 51: 865–872.PubMedCrossRefGoogle Scholar
  99. 99.
    SHIRAISHI K., NAITO K., YOSHIDA K.: Inhibition of calpain but not caspase protects the testis against injury after experimental testicular torsion of rat. Biol. Reprod., 2000, 63: 1538–1548.PubMedCrossRefGoogle Scholar
  100. 100.
    SHUTTLESWORTH G.A., DE ROOIJ D.G., HUHTANIEMI I. et al.: Enhancement of A spermatogonial proliferation and differentiation in irradiated rats by gonadotropin-releasing hormone antagonist administration. Endocrinology, 2000, 141: 37–49.PubMedCrossRefGoogle Scholar
  101. 101.
    SIMSEK F., TURKERI L., CEVIK I. et al.: Role of apoptosis in testicular tissue damage caused by varicocele. Arch. Esp. Urol., 1998, 51: 947–950.PubMedGoogle Scholar
  102. 102.
    SINHA HIKIM A.P., RAJAVASHISTH T.B., SINHA HIKIM I. et al.: Significance of apoptosis in the temporal and stage-specific loss of germ cells in the adult rat after gonadotropin deprivation. Biol. Reprod., 1997, 57: 1193–1201.PubMedCrossRefGoogle Scholar
  103. 103.
    SINHA HIKIM A.P., SWERDLOFF R.S.: Hormonal and genetic control of germ cell apoptosis in the testis. Rev. Reprod., 1999, 4: 38–47.PubMedCrossRefGoogle Scholar
  104. 104.
    SINHA HIKIM A.P., SWERDLOFF R.S.: Temporal and stagespecific changes in spermatogenesis of rat after gonadotropin deprivation by a potent gonadotropin-releasing hormone antagonist treatment. Endocrinology, 1993, 133: 2161–2170.PubMedCrossRefGoogle Scholar
  105. 105.
    SKAKKEBAEK N.E., RAJPERT-DE MEYTS E., MAIN K.M.: Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod., 2001, 16: 972–978.PubMedCrossRefGoogle Scholar
  106. 106.
    SOLARY E., EYMIN B., DROIN N. et al.: Proteases, proteolysis, and apoptosis. Cell. Biol. Toxicol., 1998, 14: 121–132.PubMedCrossRefGoogle Scholar
  107. 107.
    SRIRAMAN V., SAIRAM M.R., JAGANNADHA RAO A.: Evaluation of relative role of LH and FSH in restoration of spermatogenesis using ethanedimethylsulphonate-treated adult rats. Reprod. Biomed. Online, 2004, 8: 167–174.PubMedGoogle Scholar
  108. 108.
    SUGIHARA A., SAIKI S., TSUJI M. et al.: Expression of Fas and Fas ligand in the testes and testicular germ cell tumors: an immunohistochemical study. Anticancer Res., 1997, 17: 3861–3865.PubMedGoogle Scholar
  109. 109.
    SYLVESTER S.R., GRISWOLD M.D.: The testicular iron shuttle: a “nurse” function of the Sertoll cells. J. Androl., 1994, 15: 381–385.PubMedGoogle Scholar
  110. 110.
    SZUMIEL I.: Ionizing radiation-induced cell death. Int. J. Radiat. Biol., 1994, 66: 329–341.PubMedCrossRefGoogle Scholar
  111. 111.
    TANAKA H., FUJISAWA M., OKADA H. et al.: Apoptosis-related proteins in the testes of infertile men with varicocele. Brit. J. Urol. Int., 2002, 89: 905–909.Google Scholar
  112. 112.
    TANAKA M., SUDA T., TAKAHASHI T. et al.: Expression of the functional soluble form of human fas ligand in activated lymphocytes. Embo. J., 1995, 14: 1129–1135.PubMedGoogle Scholar
  113. 113.
    TESARIK J., MARTINEZ F., RIENZI L. et al.: In-vitro effects of FSH and testosterone withdrawal on caspase activation and DNA fragmentation in different cell types of human seminiferous epithelium. Hum. Reprod., 2002, 17: 1811–1819.PubMedCrossRefGoogle Scholar
  114. 114.
    THONNEAU P., BUJAN L., MULTIGNER L., MIEUSSET R.: Occupational heat exposure and male fertility: a review. Hum. Reprod., 1998, 13: 2122–2125.PubMedCrossRefGoogle Scholar
  115. 115.
    THORNBERRY N.A., LAZEBNIK Y.: Caspases: enemies within. Science, 1998, 281: 1312–1316.PubMedCrossRefGoogle Scholar
  116. 116.
    TILLY J.L., TILLY K.I., KENTON M.L. et al.: Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger ribonucleic acid levels. Endocrinology, 1995, 136: 232–241.PubMedCrossRefGoogle Scholar
  117. 117.
    TURNER T.T.: Acute experimental testicular torsion. No effect on the contralateral testis. J. Androl., 1985, 6: 65–72.PubMedGoogle Scholar
  118. 118.
    TURNER T.T., BROWN K.J.: Spermatic cord torsion: loss of spermatogenesis despite return of blood flow. Biol. Reprod., 1993, 49: 401–407.PubMedCrossRefGoogle Scholar
  119. 119.
    TURNER T.T., TUNG K.S., TOMOMASA H. et al.: Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol. Reprod., 1997, 57: 1267–1274.PubMedCrossRefGoogle Scholar
  120. 120.
    VAISHNAV M., MOUDGAL N.R.: Role of FSH in regulating testicular germ cell transformations in the rat: a study using DNA flow cytometry. Andrologia, 1994, 26: 111–117.PubMedGoogle Scholar
  121. 121.
    VARFOLOMEEV E.E., SCHUCHMANN M., LURIA V. et al.: Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity, 1998, 9: 267–276.PubMedCrossRefGoogle Scholar
  122. 122.
    VERGOUVEN R.P., HUISKAMP R., BAS R.J. et al.: Radiosensitivity of testicular cells in the fetal mouse. Radiat. Res., 1995, 141: 66–73.CrossRefGoogle Scholar
  123. 123.
    VIGODNER M., LEWIN L.M., SHOCHAT L. et al.: Evaluation of damage to the testicular cells of golden hamsters caused by experimental cryptorchidism using flow cytometry and confocal microscopy. Int. J. Androl., 2003, 26: 84–90.PubMedCrossRefGoogle Scholar
  124. 124.
    WANG R.A., NAKANE P.K., KOJI T.: Autonomous cell death of mouse male germ cells during fetal and postnatal period. Biol. Reprod., 1998, 58: 1250–1256.PubMedCrossRefGoogle Scholar
  125. 125.
    WANG Z.Q., TODANI T., WATANABE Y. et al.: Germ-cell degeneration in experimental unilateral cryptorchidism: role of apoptosis. Pediatr. Surg. Int., 1998, 14: 9–13.PubMedCrossRefGoogle Scholar
  126. 126.
    WATANABE M.: Characteristics of TNF alpha- and TNF beta-induced fever in the rabbit. Jpn. J. Physiol., 1992, 42: 101–116.PubMedCrossRefGoogle Scholar
  127. 127.
    WATTS L.M., HASTHORPE S., FARMER P.J. et al.: Apoptotic cell death and fertility in three unilateral cryptorchid rat models. Urol. Res., 2000, 28: 332–337.PubMedCrossRefGoogle Scholar
  128. 128.
    WEI Y.H., LEE H.C.: Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp. Biol. Med. (Maywood), 2002, 227: 671–682.Google Scholar
  129. 129.
    WENG S.L., TAYLOR S.L., MORSHEDI M. et al.: Caspase activity and apoptotic markers in ejaculated human sperm. Mol. Hum. Reprod., 2002, 8: 984–991.PubMedCrossRefGoogle Scholar
  130. 130.
    WEST A., LAHDETIE J.: X-irradiation—induced changes in the progression of type B spermatogonia and preleptotene spermatocytes. Mol. Reprod. Dev., 2001, 58: 78–87.PubMedCrossRefGoogle Scholar
  131. 131.
    WILLIAMS G.T., SMITH C.A.: Molecular regulation of apoptosis: genetic controls on cell death. Cell, 1993, 74: 777–779.PubMedCrossRefGoogle Scholar
  132. 132.
    WOOLVERIDGE I., BRYDEN A.A., TAYLOR M.F. et al.: Apoptosis and expression of apoptotic regulators in the human testis following short- and long-term anti-androgen treatment. Mol. Hum. Reprod., 1998, 4: 701–707.PubMedCrossRefGoogle Scholar
  133. 133.
    WOOLVERIDGE I., DE BOER-BROUWER M., TAYLOR M.F. et al.: Apoptosis in the rat spermatogenic epithelium following androgen withdrawal: changes in apoptosis-related genes. Biol. Reprod., 1999, 60: 461–470.PubMedCrossRefGoogle Scholar
  134. 134.
    XIA Q., ZHANG X.B., ZHANG J.: The apoptosis in damaged testicular tissue caused by varicocele. Zhonghua Nan Ke Xue, 2002, 8: 414–415.PubMedGoogle Scholar
  135. 135.
    XU J., XU Z., JIANG Y. et al.: Cryptorchidism induces mouse testicular germ cell apoptosis and changes in bcl-2 and bax protein expression. J. Environ. Pathol. Toxicol. Oncol., 2000, 19: 25–33.PubMedGoogle Scholar
  136. 136.
    YAMAMOTO C.M., SINHA HIKIM A.P., HUYNH P.N. 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: 1683–1690.PubMedCrossRefGoogle Scholar
  137. 137.
    YAN W., HUANG J.X., LAX A.S. et al.: Overexpression of Bcl-W in the testis disrupts spermatogenesis: revelation of a role of BCL-W in male germ cell cycle control. Mol. Endocrinol., 2003, 17: 1868–1879.PubMedCrossRefGoogle Scholar
  138. 138.
    YAN W., SAMSON M., JEGOU B. et al.: Bcl-w forms complexes with Bax and Bak, and elevated ratios of Bax/Bcl-w and Bak/Bcl-w correspond to spermatogonial and spermatocyte apoptosis in the testis. Mol. Endocrinol., 2000, 14: 682–699.PubMedCrossRefGoogle Scholar
  139. 139.
    YAN W., SUOMINEN J., SAMSON M. et al.: Involvement of Bcl-2 family proteins in germ cell apoptosis during testicular development in the rat and pro-survival effect of stem cell factor on germ cells in vitro. Mol. Cell. Endocrinol., 2000, 165: 115–129.PubMedCrossRefGoogle Scholar
  140. 140.
    ZAMZAMI N., BRENNER C., MARZO I. et al.: Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins. Oncogene, 1998, 16: 2265–2282.PubMedCrossRefGoogle Scholar
  141. 141.
    ZHANG Z.H., HU Z.Y., SONG X.X. et al.: Disrupted expression of intermediate filaments in the testis of rhesus monkey after experimental cryptorchidism. Int. J. Androl., 2004, 27: 234–239.PubMedCrossRefGoogle Scholar
  142. 142.
    ZHANG Z.H., JIN X., ZHANG X.S. et al.: Bcl-2 and Bax are involved in experimental cryptorchidism-induced testicular germ cell apoptosis in rhesus monkey. Contraception, 2003, 68: 297–301.PubMedCrossRefGoogle Scholar
  143. 143.
    ZHENG S. TURNER T.T., LYZIAK J.J.: Role of Caspase-2 in Germ Apoptosis During the First Phase of Spermatogenesis. Departement of Urology and Cell Biology, University of Virginia Heath Science System, Charlottesville, VA, 2005, Abstract.Google Scholar
  144. 144.
    ZINI A., ABITBOL J., SCHULSINGER D. et al.: Restoration of spermatogenesis after scrotal replacement of experimentally cryptorchid rat testis: assessment of germ cell apoptosis and eNOS expression. Urology, 1999, 53: 223–227.PubMedCrossRefGoogle Scholar
  145. 145.
    ZOU H., LI Y., LIU X. et al.: An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem., 1999, 274: 11549–11556.PubMedCrossRefGoogle Scholar

Copyright information

© Société d’Andrologie de Langue Française 2005

Authors and Affiliations

  • Souheila Amara
    • 1
  • Aline Bozec
    • 1
  • Mohamed Benahmed
    • 1
  • Claire Mauduit
    • 1
  1. 1.INSERM U 407Université Claude Bernard Lyon I, CHU, Hôpital Lyon Sud, Service Anatomie PathologiqueLyon
  2. 2.Laboratoire de Communication Cellulaire en Biologie de la Reproduction, Unité INSERM 407Faculté de Médecine Lyon-SudOullins CedexFrance

Personalised recommendations