Skip to main content
  • Apoptose, Spermatogenèse, Spermatozoïdes
  • Published:

Apoptose dans le sperme éjaculé: Revue

Apoptosis in ejaculated spermatozoa

Resume

La mort cellulaire programmée consiste en l’élimination active et régulée de cellules parfaitement identifiées, débutant pendant l’embryogenèse et se poursuivant durant la vie adulte. L’apoptose est une forme particulière de mort cellulaire programmée qui comporte des caractéristiques morphologiques et biochimiques spécifiques. L’un des rôles majeurs de l’apoptose dans les cellules somatiques est d’assurer l’élimination des cellules dangereuses, (cellules anormales, lésées et non réparables ou devenues inutiles), et de maintenir l’homéostasie au sein des tissus et organes.

La présence d’apoptose dans les spermatozoïdes éjaculés reste extrêmement controversée. La microscopie électronique a permis d’observer des spermatozoïdes présentant les caractéristiques de cellules somatiques apoptotiques dans l’éjaculat de sujets fertiles et infertiles. Cependant, il s’agit d’une technique lourde, permettant l’analyse d’un nombre limité de spermatozoïdes. De nombreux travaux soulignent l’impact de la fragmentation de l’ADN des spermatozoïdes éjaculés en AMP, sans que cette fragmentation soit reliée de façon certaine au processus apoptotique. De nouvelles techniques explorant d’autres étapes de l’apoptose, développées sur cellules somatiques, pourraient se révéler d’un intérêt majeur. Les origines et fonctions possibles de cette apoptose dans un sperme normal et en cas de pathologie seront discutées.

Abstract

It has become clear in recent years that programmed cell death occurs spontaneously in the cycle of the seminiferous epithelium. Although apoptosis is a key phenomenon in the control of sperm production, the existence and role of apoptosis in ejaculated sperm cells remain controversial.

Apoptosis — as determined by DNA fragmentation and ultrastructural analysis — is abnormally frequent in the sperm cells of the ejaculate of sterile men. In this review, we discuss the possible origins of DNA damage in ejaculated human spermatozoa and the consequences of this DNA damage when apoptotic spermatozoa are used for ICSI.

Percentages of DNA fragmentation in human ejaculated sperm are correlated with fertilization rates after IVF or ICSI assay. Detection of DNA fragmentation in human sperm could provide additional information about the biochemical integrity of sperm and may be used in future studies for fertilization failures not explained by conventional sperm parameters. However, the analysis of new markers of apoptosis (Fas, ANNEXINE V) and molecular mechanisms is now necessary to assess the role of apoptosis in human ejaculated sperm cells.

References

  1. ALVAREZ J.G., SHARMA R.K., OLLERO M. et al.: Increased DNA damage in sperm from leukocytospermic semen samples as determined by the sperm chromatin structure assay. Fertil. Steril., 2002, 2: 319–329.

    Article  Google Scholar 

  2. BACCETTI B., COLLODEL G., PIOMBONI P.: Apoptosis in human ejaculated sperm cells (notulae seminologicae 9). J. Submicrosc. Cytol. Pathol., 1996, 4: 587–596.

    Google Scholar 

  3. BACCETTI B., STREHLER E., CAPITANI S. et al.: The effect of follicle stimulating hormone therapy on human sperm structure (Notulae seminologicae 11). Hum. Reprod., 1997, 9: 1955–1968.

    Article  Google Scholar 

  4. BARROSO G., MORSHEDI M., OEHNINGER S.: Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum. Reprod., 2000, 6: 1338–1344.

    Article  Google Scholar 

  5. BLANC-LAYRAC G., BRINGUIER A.F., GUILLOT R., FELDMANN G.: Morphological and biochemical analysis of cell death in human ejaculated spermatozoa. Cell. Mol. Biol., 2000, 1: 187–197.

    Google Scholar 

  6. BLANCO-RODRIGUEZ J., MARTINEZ-GARCIA C.: Apoptosis is physiologically restricted to a specialized cytoplasmic compartment in rat spermatids. Biol. Reprod., 1999, 6: 1541–1547.

    Article  Google Scholar 

  7. CHIMINI G.: Apoptosis: repulsive encounters. Nature, 2002, 6894: 139–141.

    Article  Google Scholar 

  8. D’CRUZ O.J., DONG Y., UCKUN F.M.: Spermicidal activity of oxovanadium (IV) complexes of 1, 10-phenanthroline, 2,2′-bipyridyl, 5′-bromo-2′-hydroxyaceto-phenone and derivatives in humans. Biol. Reprod., 1999, 2: 435–444.

    Article  Google Scholar 

  9. DONNELLY E.T., MCCLURE N., LEWIS S.E.: Cryopreservation of human semen and prepared sperm: effects on motility parameters and DNA integrity. Fertil. Steril., 2001, 5: 892–900.

    Article  Google Scholar 

  10. DONNELLY E.T., O’CONNELL M., MCCLURE N., LEWIS S.E.: Differences in nuclear DNA fragmentation and mitochondrial integrity of semen and prepared human spermatozoa. Hum. Reprod., 2000, 7: 1552–1561.

    Article  Google Scholar 

  11. DURU N.K., MORSHEDI M., SCHUFFNER A., OEHNINGER S.: Cryopreservation-thawing of fractionated human spermatozoa and plasma membrane translocation of phosphatidylserine. Fertil. Steril., 2001, 2: 263–268.

    Article  Google Scholar 

  12. DURU N.K., MORSHEDI M., SCHUFFNER A., OEHNINGER S.: Semen treatment with progesterone and/or acetyl-L-carnitine does not improve sperm motility or membrane damage after cryopreservation-thawing. Fertil Steril., 2000, 4: 715–720.

    Article  Google Scholar 

  13. DURU N.K., MORSHEDI M.S., SCHUFFNER A., OEHNINGER S.: Cryopreservation-thawing of fractionated human spermatozoa is associated with membrane phosphatidylserine externalization and not DNA fragmentation. J. Androl., 2001, 4: 646–651.

    Google Scholar 

  14. DUTY S.M., SINGH N.P., RYAN L. et al.: Reliability of the comet assay in cryopreserved human sperm. Hum. Reprod., 2002, 5: 1274–1280.

    Article  Google Scholar 

  15. EVENSON D.P., LARSON K.L., JOST L.K.: Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J. Androl., 2002, 1: 25–43.

    Google Scholar 

  16. FADOK V.A., VOELKER D.R., CAMPBELL P.A., COHEN J.J., BRATTON D.L., HENSON P.M.: Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol., 1992, 7: 2207–2216.

    Google Scholar 

  17. GANDINI L., LOMBARDO F., PAOLI D. et al.: Study of apoptotic DNA fragmentation in human spermatozoa. Hum. Reprod., 2000, 4: 830–839.

    Article  Google Scholar 

  18. GLANDER H.J., SCHALLER J.: Binding of annexin V to plasma membranes of human spermatozoa: a rapid assay for detection of membrane changes after cryostorage. Mol. Hum. Reprod., 1999, 2: 109–115.

    Article  Google Scholar 

  19. GORCZYCA W., TRAGANOS F., JESIONOWSKA H., DARZYNKIEWICZ Z.: Presence of DNA strand breaks and increased sensitivity of DNAin situ to denaturation in abnormal human sperm cells: analogy to apoptosis of somatic cells. Exp. Cell. Res., 1993, 1: 202–205.

    Article  Google Scholar 

  20. GORGA F., GALDIERO M., BUOMMINO E., GALDIERO E.: Porins and lipopolysaccharide induce apoptosis in human spermatozoa. Clin. Diagn. Lab. Immunol., 2001, 1: 206–208.

    Article  Google Scholar 

  21. HASEGAWA M., ZHANG Y., NIIBE H., TERRY N.H., MEISTRICH M.L.: Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice. Radiat. Res., 1998, 3: 263–270.

    Article  Google Scholar 

  22. HIKIM A.P., WANG C., LEUNG A., SWERDLOFF R.S.: Involvement of apoptosis in the induction of germ cell degeneration in adult rats after gonadotropin-releasing hormone antagonist treatment. Endocrinology, 1995, 6: 2770–2775.

    Article  Google Scholar 

  23. HOST E., LINDENBERG S., SMIDT-JENSEN S.: The role of DNA strand breaks in human spermatozoa used for IVF and ICSI. Acta Obstet. Gynecol. Scand., 2000, 7: 559–563.

    Article  Google Scholar 

  24. HUGHES C.M., LEWIS S.E., MCKELVEY-MARTIN V.J., THOMPSON W.: A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay. Mol. Hum. Reprod., 1996, 8: 613–619.

    Article  Google Scholar 

  25. 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, 2: 393–399.

    Article  Google Scholar 

  26. IRVINE D.S., TWIGG J.P., GORDON E.L., FULTON N., MILNE P.A., AITKEN R.J.: DNA integrity in human spermatozoa: relationships with semen quality. J. Androl., 2000, 1: 33–44.

    Google Scholar 

  27. TO K., TANEMURA K., GOTOH H., KUROHMARU M., HAYASHI Y.: Apoptosis-like cell death in experimentally-induced cryptorchidism in adult mice. J. Vet. Med. Sci., 1997, 5: 353–359.

    Google Scholar 

  28. JOHNSON L., CHATURVEDI P.K., WILLIAMS J.D.: Missing generations of spermatocytes and spermatids in seminiferous epithelium contribute to low efficiency of spermatogenesis in humans. Biol. Reprod., 1992, 6: 1091–1098.

    Article  Google Scholar 

  29. JOZA N., KROEMER G., PENNINGER J.M.: Genetic analysis of the mammalian cell death machinery. Trends Genet., 2002, 3: 142–149.

    Article  Google Scholar 

  30. KERR J.B.: Spontaneous degeneration of germ cells in normal rat testis: assessment of cell types and frequency during the spermatogenic cycle. J. Reprod. Fertil., 1992, 3: 825–830.

    Google Scholar 

  31. LARSON K.L., BRANNIAN J.D., TIMM B.K., JOST L.K., EVENSON D.P.: Density gradient centrifugation and glass wool filtration of semen remove spermatozoa with damaged chromatin structure. Hum. Reprod., 1999, 8: 2015–2019.

    Article  Google Scholar 

  32. LEVY R., SEIFER-AKNIN I.: Apoptose au cours de la spermatogenèse et dans le sperme éjaculé. Ann. Biol. Clin. (Paris), 2001, 5: 531–545.

    Google Scholar 

  33. LOPES S., JURISICOVA A., SUN J.G., CASPER R.F.: Reactive oxygen species: potential cause for DNA fragmentation in human spermatozoa. Hum. Reprod., 1998, 4: 896–900.

    Article  Google Scholar 

  34. LOPES S., SUN J.G., JURISICOVA A., MERIANO J., CASPER R.F.: Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen samples and correlates with failed fertilization in intracytoplasmic sperm injection. Fertil. Steril., 1998, 3: 528–532.

    Article  Google Scholar 

  35. MANICARDI G.C., TOMBACCO A., BIZZARO D., BIANCHI U., BIANCHI P.G., SAKKAS D.: DNA strand breaks in ejaculated human spermatozoa: comparison of susceptibility to the nick translation and terminal transferase assays. Histochem. J., 1998, 1: 33–39.

    Article  Google Scholar 

  36. MANN S.L., PATTON W.C., KING A., CHAN P.J.: Comparative genomic hybridization analysis of sperm DNA apoptosis after exposure to heat shock. J. Assist. Reprod. Genet., 2002, 4: 195–200.

    Article  Google Scholar 

  37. MARCHETTI C., OBERT G., DEFFOSEZ A., FORMSTECHER P., MARCHETTI P.: Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Hum. Reprod., 2002, 5: 1257–1265.

    Article  Google Scholar 

  38. MOOR A.C.: Signaling pathways in cell death and survival after photodynamic therapy. J. Photochem. Photobiol. B, 2000, 1: 1–13.

    Article  Google Scholar 

  39. MORRIS I.D., ILOTT S., DIXON L., BRISON D.R.: The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development. Hum. Reprod., 2002, 4: 990–998.

    Article  Google Scholar 

  40. MURATORI M., PIOMBONI P., BALDI E. et al.: Functional and ultrastructural features of DNA-fragmented human sperm. J. Androl., 2000, 6: 903–912.

    Google Scholar 

  41. NAKAGAWA S., NAKAMURA N., FUJIOKA M., MORI C.: Spermatogenic cell apoptosis induced by mitomycin C in the mouse testis. Toxicol. Appl. Pharmacol., 1997, 2: 204–213.

    Article  Google Scholar 

  42. PERERA D., PIZZEY A., CAMPBELL A. et al.: Sperm DNA damage in potentially fertile homozygous beta-thalassaemia patients with iron overload. Hum. Reprod., 2002, 7: 1820–1825.

    Article  Google Scholar 

  43. RAFF M.C.: Social controls on cell survival and cell death. Nature, 1992, 6368: 397–400.

    Article  Google Scholar 

  44. RICCI G., PERTICARARI S., FRAGONAS E. et al.: Apoptosis in human sperm: its correlation with semen quality and the presence of leukocytes. Hum. Reprod., 2002, 10: 2665–2672.

    Article  Google Scholar 

  45. ROYERE D., GUERIF F., ROCHEREAU DE REVIERS M.T., PANTHIER S., LANSAC J.: Apoptose dans les gonades mâles. Contracept. Fertil. Sex., 1998, 7–8: 517–521.

    Google Scholar 

  46. SAKKAS D., MANICARDI G.C., TOMLINSON M. et al.: The use of two density gradient centrifugation techniques and the swim-up method to separate spermatozoa with chromatin and nuclear DNA anomalies. Hum. Reprod., 2000, 5: 1112–1116.

    Article  Google Scholar 

  47. SAKKAS D., MARIETHOZ E., MANICARDI G., BIZZARO D., BIANCHI P.G., BIANCHI U.: Origin of DNA damage in ejaculated human spermatozoa. Rev. Reprod., 1999, 1: 31–37.

    Article  Google Scholar 

  48. SAKKAS D., MARIETHOZ E., ST JOHN J.C.: Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the Fas-mediated pathway. Exp. Cell. Res., 1999, 2: 350–355.

    Article  Google Scholar 

  49. SAKKAS D., MOFFATT O., MANICARDI G.C., MARIETHOZ E., TAROZZI N., BIZZARO D.: Nature of DNA damage in ejaculated human spermatozoa and the possible involvement of apoptosis. Biol. Reprod., 2002, 4: 1061–1067.

    Article  Google Scholar 

  50. SHEN H.M., DAI J., CHIA S.E., LIM A., ONG C.N.: Detection of apoptotic alterations in sperm in subfertile patients and their correlations with sperm quality. Hum. Reprod., 2002, 5: 1266–1273.

    Article  Google Scholar 

  51. SHIN J.H., MORI C., SHIOTA K.: Involvement of germ cell apoptosis in the induction of testicular toxicity following hydroxyurea treatment. Toxicol. Appl. Pharmacol., 1999, 2: 139–149.

    Article  Google Scholar 

  52. SHIRAISHI K., YOSHIDA K., FUJIMIYA T., NAITO K.: Activation of mitogen activated protein kinases and apoptosis of germ cells after vasectomy in the rat. J. Urol., 2002, 3: 1273–1278.

    Google Scholar 

  53. SINGH N.P., DANNER D.B., TICE R.R., MCCOY M.T., COLLINS G.D., SCHNEIDER E.L.: Abundant alkali-sensitive sites in DNA of human and mouse sperm. Exp. Cell. Res., 1989, 2: 461–470.

    Article  Google Scholar 

  54. SUN J.G., JURISICOVA A., CASPER R.F.: Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilizationin vitro. Biol. Reprod., 1997, 3: 602–607.

    Article  Google Scholar 

  55. SUTOVSKY P., NEUBER E., SCHATTEN G.: Ubiquitin-dependent sperm quality control mechanism recognizes spermatozoa with DNA defects as revealed by dual ubiquitin-TUNEL assay. Mol. Reprod. Dev., 2002, 3: 406–413.

    Article  Google Scholar 

  56. 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, 7: 1811–1819.

    Article  Google Scholar 

  57. VAN LOO G., VAN GURP M., DEPUYDT B. et al.: The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ., 2002, 1: 20–26.

    Google Scholar 

  58. VERMES I., HAANEN C., STEFFENS-NAKKEN H., REUTELINGSPERGER C.: A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J. Immunol. Methods, 1995, 1: 39–51.

    Article  Google Scholar 

  59. WEIL M., JACOBSON M.D., RAFF M.C.: Are caspases involved in the death of cells with a transcriptionally inactive nucleus ? Sperm and chicken erythrocytes. J. Cell Sci., 1998, Pt 18: 2707–2715.

    Google Scholar 

  60. WENG S.L., TAYLOR S.L., MORSHEDI M. et al.: Caspase activity and apoptotic markers in ejaculated human sperm. Mol. Hum. Reprod., 2002, 11: 984–991.

    Article  Google Scholar 

  61. WYLLIE A.H., KERR J.F., CURRIE A.R.: Cell death: the significance of apoptosis. Int. Rev. Cytol., 1980, 68: 251–306.

    Article  PubMed  CAS  Google Scholar 

  62. YOUNGLAI E.V., HOLT D., BROWN P., JURISICOVA A., CASPER R.F.: Sperm swim-up techniques and DNA fragmentation. Hum. Reprod., 2001, 9: 1950–1953.

    Article  Google Scholar 

  63. ZINI A., BIELECKI R., PHANG D., ZENZES M.T.: Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil. Steril., 2001, 4: 674–677.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rachel Levy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, G., Sabido, O., Laurent, J.L. et al. Apoptose dans le sperme éjaculé: Revue. Androl. 13, 217–227 (2003). https://doi.org/10.1007/BF03034875

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03034875

Mots clés

Key-Words