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  • Fertilité Après Traitement Anti-Cancéreux
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Cryoconservation du tissue testiculaire chez l’enfant: comment préserver la fertilité chez le jeune garçon?

Cryopreservation of testicular tissue in boys: how can the boy’s fertility be preserved?

Andrologie volume 14, pages 404–411 (2004)Cite this article

Resume

La prise en charge thérapeutique des cancers de l’enfant s’est considérablement améliorée depuis les trente dernières années avec un taux de survie à long terme atteignant les 70%. Cependant, l’amélioration de l’efficacité thérapeutique s’associe à une augmentation des effets indésirables. Parmi les effets morbides, la toxicité sur le tissue gonadique est la plus fréquemment rencontrée et peut entraîner une stérilité définitive à l’âge adulte.

La préservation de la fertilité de l’enfant doit être envisagée avant le début des traitements. Ainsi, chez la petite fille, la congélation et conservation du tissu ovarien s’est mise en place en France depuis quelques années. Chez le jeune garçon pubère, il est possible de proposer une autoconservation de spermatozoïdes obtenus dans un recueil après masturbation.

Cependant, chez le garçon pré pubère ou en cas d’échec au recueil de sperme, une autre stratégie de prise en charge doit être envisagée, elle implique en premier lieu le prélèvement chirurgical du tissue testiculaire avec deux options possible: i) la congélation du tissue testiculaire entier ou ii) la congélation de cellules germinales immatures et/ou de cellules germinales matures (spermatozoïdes).

L’utilisation ultérieure du tissue testiculaire immature cryoconservé pourra s’effectuer soit après maturationin vitro des cellules germinales (spermatogenèsein vitro), soit par transplantation des cellules germinales par greffe autologue voire xénogreffe. Le risque de la greffe autologue est la réintroduction de l’affection maligne chez le patient, alors que la xénogreffe élimine ce risque. Cependant, cette dernière approche soulève d’autres interrogations à la fois d’ordre éthique et biologique.

Abstract

Survival rates for almost all types of childhood cancer have improved over the last 30 years. Estimates suggest that, in 2010, 1 out of 715 adolescents and young adults will be a long-term survivor of childhood cancer. With current therapy, 70% of children are cured. The increased number of survivors has focused attention on the many long-term or late sequelae of treatment. Most of the effects cannot be detected at the end of therapy, but only become apparent with puberty, growth and the normal aging process. Among the various sequelae, gonadal dysfunction is observed and the degree of gonadal damage depends on the type and total doses of chemotherapy and/or radiotherapy. The male gonald is also more sensitive to cancer therapy than the female gonad.

Cryopreservation of ejaculated spermatozoa should be proposed for sexually mature boys. However, when ejaculated semen samples cannot be collected, or in the case of prepubertal boys who are not yet able to produce spermatozoa, another strategy must be used: testicular biopsy associated with cryopreservation of (i) testicular tissue, or (ii) isolated testicular spermatozoa or (iii) immature germ cells. The future use of immature testicular tissue will depend on the development of novel technologies in humans such as germ cellin vitro maturation, or autologous or xenogeneic germ cell transplantation.

References

  1. BAHADUR G., CHATTERJEE R., RALPH D.: Testicular tissue cryopreservation in boys. Ethical and legal issues: case report. Hum. Reprod., 2000, 15: 1416–1420.

    Article  PubMed  CAS  Google Scholar 

  2. BAHADUR G., LING K.L., HART R. et al.: Semen production in adolescent cancer patients. Hum. Reprod., 2002, 17: 2654–2656.

    Article  PubMed  CAS  Google Scholar 

  3. BAHADUR G., LING K.L., HART R. et al.: Semen quality and cryopreservation in adolescent cancer patients. Hum. Reprod., 2002, 17: 3157–3161.

    Article  PubMed  CAS  Google Scholar 

  4. BIRCH J.M., MARSDEN H.B., JONES P.H., PEARSON D., BLAIR V.: Improvements in survival from childhood cancer: results of a population based survey over 30 years. Br. Med. J. (Clin. Res. Ed.), 1988, 296: 1372–1376.

    Article  CAS  Google Scholar 

  5. BIRCH J.M., ALSTON R.D., QUINN M., KELSEY A.M.: Incidence of malignant disease by morphological type, in young persons aged 12–24 years in England, 1979–1997. Eur. J. Cancer, 2003, 39: 2622–2631.

    Article  PubMed  CAS  Google Scholar 

  6. BIRCH J.M., ALSTON R.D., KELSEY A.M. et al.: Classification and incidence of cancers in adolescents and young adults in England 1979–1997. Br. J. Cancer, 2002, 87: 1267–1274.

    Article  PubMed  CAS  Google Scholar 

  7. BRINSTER R.L., ZIMMERMANN J.W.: Spermatogenesis following male germ-cell transplantation. Proc. Natl. Acad. Sci. (USA), 1994, 91: 11298–11302.

    Article  CAS  Google Scholar 

  8. BROOK P.F., RADFORD J.A., SHALET S.M., JOYCE A.D., GOSDEN R.G.: Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation. Fertil. Steril., 2001, 75: 269–274.

    Article  PubMed  CAS  Google Scholar 

  9. BROUGHAM M.F., KELNAR C.J., SHARPE R.M., WALLACE W.H.: Male fertility following childhood cancer: current concepts and future therapies. Asian J. Androl., 2003, 5: 325–337.

    PubMed  Google Scholar 

  10. CENTOLA G.M., KELLER J.W., HENZLER M., RUBIN P.: Effect of low-dose testicular irradiation on sperm count and fertility in patients with testicular seminoma. J. Androl., 1994, 15: 608–613.

    PubMed  CAS  Google Scholar 

  11. CLIFTON D.K., BREMNER W.J.: The effect of testicular x-irradiation on spermatogenesis in man. A comparison with the mouse. J. Androl., 1983, 4: 387–392.

    PubMed  CAS  Google Scholar 

  12. CLOUTHIER D.E., AVARBOCK M.R., MAIKA S.D., HAMMER R.E., BRINSTER R.L.: Rat spermatogenesis in mouse testis. Nature, 1996, 381: 418–421.

    Article  PubMed  CAS  Google Scholar 

  13. CREMADES N., BERNABEU R., BARROS A., SOUSA M.:In vitro maturation of round spermatids using co-culture on Vero cells. Hum. Reprod., 1999, 14: 1287–1293.

    Article  PubMed  CAS  Google Scholar 

  14. DE ROOIJ D.G., GROOTEGOED J.A.: Spermatogonial stem cells. Curr. Opin. Cell Biol., 1998, 10: 694–701.

    Article  PubMed  Google Scholar 

  15. FENG L.X., CHEN Y., DETTIN L. et al.: Generation andin vitro differentiation of a spermatogonial cell line. Science, 2002, 297: 392–395.

    Article  PubMed  CAS  Google Scholar 

  16. FISHEL S., ASLAM I., TESARIK J.: Spermatid conception: a stage too early, or a time too soon? Hum. Reprod., 1996, 11: 1371–1375.

    PubMed  CAS  Google Scholar 

  17. FREDERICKX V., MICHIELS A., GOOSSENS E. et al.: Recovery, survival and functional evaluation by transplantation of frozen-thawed mouse germ cells. Hum. Reprod., 2004, 19: 948–953.

    Article  PubMed  CAS  Google Scholar 

  18. GIUILI G., TOMLJENOVIC A., LABRECQUE N. et al.: Murine spermatogonial stem cells: targeted transgene expression and purification in an active state. EMBO Rep., 2002, 3: 753–759.

    Article  PubMed  CAS  Google Scholar 

  19. GRUNDY R., GOSDEN R.G., HEWITT M. et al.: Fertility preservation for children treated for cancer (1): scientific advances and research dilemmas. Arch. Dis. Child., 2001, 84: 355–359.

    Article  PubMed  CAS  Google Scholar 

  20. HOVATTA O., SILYE R., KRAUSZ T. et al.: Cryopreservation of human ovarian tissue using dimethylsulphoxide and propanediol-sucrose as cryoprotectants. Hum. Reprod., 1996, 11: 1268–1272.

    PubMed  CAS  Google Scholar 

  21. HOVATTA O.: Cryopreservation of testicular tissue in young cancer patients. Hum. Reprod. Update, 2001, 7: 378–383.

    Article  PubMed  CAS  Google Scholar 

  22. HUE D., STAUB C., PERRARD-SAPORI M.H. et al.: Meiotic differentiation of germinal cells in three-week cultures of whole cell population from rat seminiferous tubules. Biol. Reprod., 1998, 59: 379–387.

    Article  PubMed  CAS  Google Scholar 

  23. IZADYAR F., MATTHIJS-RIJSENBILT J.J., DEN OUDEN K. et al.: Development of a cryopreservation protocol for type A spermatogonia. J. Androl., 2002, 23: 537–545.

    PubMed  CAS  Google Scholar 

  24. JAHNUKAINEN K., HOU M., PETERSEN C. et al.: Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. Cancer. Res. 2001, 61(2): 706–710.

    PubMed  CAS  Google Scholar 

  25. KANATSU-SHINOHARA M., OGONUKI N., INOUE K. et al.: Restoration of fertility in infertile mice by transplantation of cryopreserved male germline stem cells. Hum. Reprod., 2003, 18: 2660–2667.

    Article  PubMed  CAS  Google Scholar 

  26. LACHAM-KAPLAN O.: In vivo and in vitro differentiation of male germ cells in the mouse. Reproduction, 2004, 128: 147–152.

    Article  PubMed  Google Scholar 

  27. LITTLEY M.D., SHALET S.M., BEARDWELL C.G., ROBINSON E.L., SUTTON M.L.: Radiation-induced hypopituitarism is dose-dependent. Clin. Endocrinol. (Oxf), 1989, 31: 363–373.

    Article  CAS  Google Scholar 

  28. MCLEAN D.J., RUSSELL L.D., GRISWOLD M.D.: Biological activity and enrichment of spermatogonial stem cells in vitamin A-deficient and hyperthermia-exposed testes from mice based on colonization following germ cell transplantation. Biol. Reprod., 2002, 66: 1374–1379.

    Article  PubMed  CAS  Google Scholar 

  29. MEACHEM S., VON SCHONFELDT V., SCHLATT S.: Spermatogonia: stem cells with a great perspective. Reproduction, 2001, 121: 825–834.

    Article  PubMed  CAS  Google Scholar 

  30. MEISTRICH M.L., WILSON G., KANGASNIEMI M., HUHTANIEMI I.: Mechanism of protection of rat spermatogenesis by hormonal pretreatment: stimulation of spermatogonial differentiation after irradiation. J. Androl., 2000, 21: 464–469.

    PubMed  CAS  Google Scholar 

  31. MEISTRICH M.L., SHETTY G.: Suppression of testosterone stimulates recovery of spermatogenesis after cancer treatment. Int. J. Androl., 2003, 26: 141–146.

    Article  PubMed  CAS  Google Scholar 

  32. MERTENS A.C., YASUI Y., NEGLIA J.P. et al.: Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J. Clin. Oncol., 2001, 19: 3163–3172.

    PubMed  CAS  Google Scholar 

  33. MULLER J., SKAKKEBAEK N.E.: Quantification of germ cells and seminiferous tubules by stereological examination of testicles from 50 boys who suffered from sudden death. Int. J. Androl., 1983, 6: 143–156.

    Article  PubMed  CAS  Google Scholar 

  34. MULLER J., SONKSEN J., SOMMER P. et al.: Cryopreservation of semen from pubertal boys with cancer. Med. Pediatr. Oncol., 2000, 34: 191–194.

    Article  PubMed  CAS  Google Scholar 

  35. NAGANO M., AVARBOCK M.R., LEONIDA E.B., BRINSTER C.J., BRINSTER R.L.: Culture of mouse spermatogonial stem cells. Tissue Cell, 1998, 30: 389–397.

    Article  PubMed  CAS  Google Scholar 

  36. NAGANO M., MCCARREY J.R., BRINSTER R.L.: Primate spermatogonial stem cells colonize mouse testes. Biol. Reprod., 2001, 64: 1409–1416.

    Article  PubMed  CAS  Google Scholar 

  37. NAGANO M., PATRIZIO P., BRINSTER R.L.: Long-term survival of human spermatogonial stem cells in mouse testes. Fertil. Steril., 2002, 78: 1225–1233.

    Article  PubMed  Google Scholar 

  38. NISTAL M., PANIAGUA R.: Occurrence of primary spermatocytes in the infant and child testis. Andrologia, 1984, 16: 532–536.

    Article  PubMed  CAS  Google Scholar 

  39. OEFFINGER K.C., HUDSON M.M.: Long-term complications following childhood and adolescent cancer: foundations for providing risk-based health care for survivors. CA Cancer J. Clin., 2004, 54: 208–236.

    Article  PubMed  Google Scholar 

  40. OGAWA T., DOBRINSKI I., AVARBOCK M.R., BRINSTER R.L.: Xenogeneic spermatogenesis following transplantation of hamster germ cells to mouse testes. Biol. Reprod., 1999, 60: 515–521.

    Article  PubMed  CAS  Google Scholar 

  41. PARKS J.E., LEE D.R., HUANG S., KAPROTH M.T.: Prospects for spermatogenesis in vitro. Theriogenology, 2003, 59: 73–86.

    Article  PubMed  CAS  Google Scholar 

  42. POSTOVSKY S., LIGHTMAN A., AMINPOUR D. et al.: Sperm cryopreservation in adolescents with newly diagnosed cancer. Med. Pediatr. Oncol., 2003, 40: 355–359.

    Article  PubMed  Google Scholar 

  43. REMONTET L., ESTEVE J., BOUVIER A.M. et al.: Cancer incidence and mortality in France over the period 1978–2000. Rev. Épidemiol. Santé Publique, 2003, 51: 3–30.

    PubMed  CAS  Google Scholar 

  44. RIVES N.: Comment identifier le spermatozoide vivant? Andrologie, 2002, 12: 332–341.

    Article  Google Scholar 

  45. SANDERS J.E., HAWLEY J., LEVY W. et al.: Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood, 1996, 87: 3045–3052.

    PubMed  CAS  Google Scholar 

  46. SCHLATT S., ROSIEPEN G., WEINBAUER G.F. et al.: Germ cell transfer into rat, bovine, monkey and human testes. Hum. Reprod., 1999, 14: 144–150.

    Article  PubMed  CAS  Google Scholar 

  47. SCHLATT S.: Spermatogonial stem cell preservation and transplantation. Mol. Cell. Endocrinol., 2002, 187: 107–111.

    Article  PubMed  CAS  Google Scholar 

  48. SCHLATT S.: Germ cell transplantation. Mol. Cell. Endocrinol., 2002, 186: 163–167.

    Article  PubMed  CAS  Google Scholar 

  49. SCHMIEGELOW M.L., SOMMER P., CARLSEN E. et al.: Penile vibratory stimulation and electroejaculation before anticancer therapy in two pubertal boys. J. Pediatr. Hematol. Oncol., 1998, 20: 429–430.

    Article  PubMed  CAS  Google Scholar 

  50. SHALET S.M., TSATSOULIS A., WHITEHEAD E., READ G.: Vulnerability of the human Leydig cell to radiation damage is dependent upon age. J. Endocrinol., 1989, 120: 161–165.

    Article  PubMed  CAS  Google Scholar 

  51. SHINOHARA T., AVARBOCK M.R., BRINSTER R.L.: Beta1-and alpha6-integrin are surface markers on mouse spermatogonial stem cells. Proc. Natl. Acad. Sci. (USA), 1999, 96: 5504–5509.

    Article  CAS  Google Scholar 

  52. SHINOHARA T., INOUE K., OGONUKI N. et al.: Birth of offspring following transplantation of cryopreserved immature testicular pieces andin vitro microinsemination. Hum. Reprod., 2002, 17: 3039–3045.

    Article  PubMed  CAS  Google Scholar 

  53. SOFIKITIS N., MANTZAVINOS T., LOUTRADIS D. et al.: Ooplasmic injections of secondary spermatocytes for non-obstructive azoospermia. Lancet, 1998, 351: 1177–1178.

    Article  PubMed  CAS  Google Scholar 

  54. SOMMELET D., LACOUR B., CLAVEL J.: Epidémiologie des cancers de l’enfant. Bull. Acad. Natl. Med., 2003, 187: 711–737.

    PubMed  Google Scholar 

  55. SPEISER B., RUBIN P., CASARETT G.: Aspermia following lower truncal irradiation in Hodgkin’s disease. Cancer, 1973, 32: 692–698.

    Article  PubMed  CAS  Google Scholar 

  56. SPRADLING A., DRUMMOND-BARBOSA D., KAI T.: Stem cells find their niche. Nature, 2001, 414: 98–104.

    Article  PubMed  CAS  Google Scholar 

  57. STAUB C., HUE D., NICOLLE J.C. et al.: The whole meiotic process can occur in vitro in untransformed rat spermatogenic cells. Exp. Cell. Res., 2000, 260: 85–95.

    Article  PubMed  CAS  Google Scholar 

  58. TESARIK J.: Fertilization of oocytes by injecting spermatozoa, spermatids and spermatocytes. Rev. Reprod., 1996, 1: 149–152.

    Article  PubMed  CAS  Google Scholar 

  59. TESARIK J., GUIDO M., MENDOZA C., GRECO E.: Human spermatogenesis in vitro: respective effects of follicle-stimulating hormone and testosterone on meiosis, spermiogenesis, and Sertoli cell apoptosis. J. Clin. Endocrinol. Metab., 1998, 83: 4467–4473.

    Article  PubMed  CAS  Google Scholar 

  60. TESARIK J., MENDOZA C., GRECO E.:In vitro maturation of immature human male germ cells. Mol. Cell. Endocrinol., 2000, 166: 45–50.

    Article  PubMed  CAS  Google Scholar 

  61. THOMSON A.B., CRITCHLEY H.O., WALLACE W.H.: Fertility and progeny. Eur. J. Cancer, 2002, 38: 1634–1644.

    Article  PubMed  CAS  Google Scholar 

  62. VAN DER WEE K.S., JOHNSON E.W., DIRAMI G., DYM T.M., HOFMANN M.C.: Immunomagnetic isolation and long-term culture of mouse type A spermatogonia. J. Androl., 2001, 22: 696–704.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratoire de Biologie de la Reproduction-CECOS, CHU Charles Nicolle, 1 rue de Germont, 76031, Rouen

    Nathalie Rives & Bertrand Macé

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  1. Nathalie Rives
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  2. Bertrand Macé
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Correspondence to Nathalie Rives.

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Communication au Colloque de la Fédération des CECOS, Lyon, 18 mars 2004.

Préserver la fertilité des patients soumis à des traitements anticancéreux: la cryopréservation des gamètes et du tissu gonadique.

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Rives, N., Macé, B. Cryoconservation du tissue testiculaire chez l’enfant: comment préserver la fertilité chez le jeune garçon?. Androl. 14, 404–411 (2004). https://doi.org/10.1007/BF03035172

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Basic and Clinical Andrology

ISSN: 2051-4190