Spermatogonial stem cell preservation and transplantation: From research to clinic

Human Reproduction

Volumn 28, Issue 4, 2013, Pages 897-907

  Goossens, E ^a   Van Saen, D ^b   Tournaye, H ^a,b  

^a VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^b CENTRE FOR REPRODUCTIVE MEDICINE   (Belgium)

Author keywords

clinic; fertility; prepubertal boys; spermatogonial stem cell; transplantation

Indexed keywords

ALPHA1 INTEGRIN; BUSULFAN; CD133 ANTIGEN; CHLORAMBUCIL; CYCLOPHOSPHAMIDE; HYDROXYUREA; IFOSFAMIDE; MELPHALAN; PROCARBAZINE; STAGE SPECIFIC EMBRYO ANTIGEN 4;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANDROGEN SYNTHESIS; ARTICLE; AZOOSPERMIA; BLASTOCYST; BONE MARROW TRANSPLANTATION; CANCER CELL; CELL MATURATION; CELL SUSPENSION; CHILDHOOD CANCER; CHROMOSOME ABERRATION; CRYOPRESERVATION; FOLLITROPIN BLOOD LEVEL; HUMAN; HYALINE DEGENERATION; KLINEFELTER SYNDROME; MASTURBATION; NONHUMAN; OLIGOSPERMIA; PHAGOCYTOSIS; REPRODUCTIVE PROCEDURE; SAFETY; SEDIMENTATION RATE; SEMINIFEROUS TUBULE; SPERMATOGENESIS; SPERMATOGONIAL STEM CELL PRESERVATION; SPERMATOGONIAL STEM CELL TRANSPLANTATION; STEM CELL TRANSPLANTATION; SYSTEMATIC REVIEW; TESTICULAR SPERM EXTRACTION; TESTIS; TESTIS BIOPSY; TISSUE GRAFT; VITRIFICATION;

EID: 84875601624     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/det039     Document Type: Article

References (101)

1. Abrishami M, Abbasi S, Honaramooz A. The effect of donor age on progression of spermatogenesis in canine testicular tissue after xenografting into immunodeficient mice. Theriogenology 2010; 73: 512-522.
2. Aksglaede L, Wikstro AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A. Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update 2006; 12: 39-48.
3. Avarbock MR, Brinster CJ, Brinster RL. Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat Med 1996; 2: 693-696.
4. Baert Y, Goossens E, van Saen D, Ning L, In't Veld P, Tournaye H. Orthotopic grafting of cryopreserved prepubertal testicular tissue: in search of a simple yet effective cryopreservation protocol. Fertil Steril 2012; 97: 1152-1157.e1-2.
5. Baert Y, Goossens E, Van Saen D, Ning L, Haentjens P, Tournaye H. Comparison of different cooling rates using cryoprotective DMSO for long-term storage of human testicular tissue. submitted for publication. Bahadur G, Ralph D. Gonadal tissue cryopreservation in boys with paediatric cancers. Hum Reprod 1999; 14: 11-17.
6. Bar-Shira Maymon B, Yogev L, Marks A, Hauser R, Botchan A, Yavetz H. Sertoli cell inactivation by cytotoxic damage to the human testis after cancer chemotherapy. Fertil Steril 2004; 81: 1391-1394.
7. Berthaut I, Guignedoux G, Kirsch-Noir F, de Larouzier V, Ravel C, Bachir D, Galacteos F, Ancel P, Kunstmann J, Levy L et al. Influence of sickle cell disease and treatment with hydroxyurea on sperm parameters and fertility of human males. Haematologica 2008; 93: 988-993.
8. Boyle PF, Fox M, Slater D. Transplantation of interstitial cells of the testis: effect of implant site, graft mass and ischaemia. Br J Urol 1975; 47: 891-898.
9. Brackett NL. Semen retrieval by penile vibratory stimulation in men with spinal cord injury. Hum Reprod Update 1999; 5: 216-222.
10. Brinster RL, Zimmermann JW. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci USA 1994; 91: 11298-11302.
11. Caires KC, de Avila J, McLean DJ. Vascular endothelial growth factor regulates germ cell survival during establishment of spermatogenesis in the bovine testis. Reproduction 2009; 138: 667-677.
12. Caires KC, de Avila JM, Cupp AS, McLean DJ. VEGFA family isoforms regulate SSC homeostasis in-vivo. Endocrinology 2012; 153: 887-900.
13. Chan KW, Wood BJ, Johnson HW. Testicular adhesion: a potential complication from wedge testicular biopsy in childhood leukemia. Med Pediatr Oncol 1988; 16: 366-367.
14. Chapman LE. Xenotransplantation, xenogeneic infections, biotechnology, and public health. Mt Sinai J Med 2009; 76: 435-441.
15. Curaba M, Poels J, van Langendonckt A, Donnez J, Wyns C. Can prepubertal human testicular tissue be cryopreserved by vitrification. Fertil Steril 2011; 95: 2123.e9-2123.e
16. Dirami G, Ravindranath N, Pursel V, Dym M. Effects of stem cell factor and granulocyte macrophage-colony stimulating factor on survival of porcine type A spermatogonia cultured in KSOM. Biol Reprod 1999; 61: 225-230.
17. Dolmans M, Marinescu C, Saussoy P, Van Langendonckt A, Amorim C, Donnez J. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood 2010; 116: 2908-2914.
18. Dym M, Kokkinaki M, He Z. SSCs: mouse and human comparisons. Birth Defects Res C Embryo Today 2009; 87: 27-34.
19. Frederickx V, Michiels A, Goossens E, De Block G, Van Steirteghem AC, Tournaye H. Recovery, survival and functional evaluation by transplantation of frozen-thawed mouse germ cells. Hum Reprod 2004; 19: 948-953.
20. Friedler S, Raziel A, Strassburger D, Schachter M, Bern O, Ron-El R. Outcome of ICSI using fresh and cryopreserved-thawed testicular spermatozoa in patients with non-mosaic Klinefelter's syndrome. Hum Reprod 2001; 6: 318-321.
21. Fujita K, Tsujimura A, Miyagawa Y, Kiuchi H, Matsuoka Y, Takao T, Takada S, Nonomura N, Okuyama A. Isolation of germ cells from leukemia and lymphoma cells in a human in-vitro model: potential clinical application for restoring human fertility after anticancer therapy. Cancer Res 2006; 66: 11166-11171.
22. Geens M, Van de Velde H, De Block G, Goossens E, Van Steirteghem A, Tournaye H. The efficiency of magnetic-activated cell sorting and fluorescence-activated cell sorting in the decontamination of testicular cell suspensions in cancer patients. Hum Reprod 2007; 22: 733-742.
23. Geens M, Goossens E, Tournaye H. Cell selection by selective matrix adhesion is not sufficiently efficient for complete malignant cell depletion from contaminated human testicular cell suspensions. Fertil Steril 2011; 95: 787-791.
24. Gies I, De Schepper J, Van Saen D, Anckaert E, Goossens E, Tournaye H. Failure of a combined clinical-and hormonal-based strategy to detect early spermatogenesis and retrieve spermatogonial stem cells in 47, XXY boys by single testicular biopsy. Hum Reprod 2012; 27: 998-1004.
25. Goossens E, Frederickx V, De Block G, Van Steirteghem AC, Tournaye H. Reproductive capacity of sperm obtained after germ cell transplantation in a mouse model. Hum Reprod 2003; 18: 1874-1880.
26. Goossens E, Geens M, De Block G, Tournaye H. Spermatogonial survival in long-term human prepubertal xenografts. Fertil Steril 2008a; 90: 2019-2022.
27. Goossens E, De Block G, Tournaye H. Computer-assisted motility analysis of spermatozoa obtained after SSC transplantation in the mouse. Fertil Steril 2008b; 90: 1411-1416.
28. Goossens E, De Rycke M, Haentjens P, Tournaye H. DNA methylation patterns of spermatozoa and two generations of offspring obtained after murine SSC transplantation. Hum Reprod 2009; 24: 2255-2263.
29. Goossens E, de Vos P, Tournaye H. Array comparative genomic hybridization analysis does not show genetic alterations in spermatozoa and offspring generated after SSC transplantation in the mouse. Hum Reprod 2010; 25: 1836-1842.
30. Goossens E, Bilgec T, Van Saen D, Tournaye H. Mouse germ cells go through typical epigenetic modifications after intratesticular tissue grafting. Hum Reprod 2011; 26: 3388-3400.
31. Hermann BP, Sukhwani M, Salati J, Sheng Y, Chu T, Orwig KE. Seperating spermatogonia from cancer cells in contaminated prepubertal primate testis cell suspensions. Hum Reprod 2011; 26: 3222-3231.
32. Hermann BP, Sukhwani M, Winkler F, Pascarella JN, Peters KA, Sheng Y, Valli H, Rodriguez M, Ezzelarab M, Dargo G et al. Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm. Cell Stem Cell 2012; 11: 715-726.
33. Holmes DI, Zachary I. The vascular endothelial growth factor (VEGF) family: angiogenic factors in health and disease. Genome Biol 2005; 6: 209.
34. Honaramooz A, Megee SO, Dobrinski I. Germ cell transplantation in pigs. Biol Reprod 2002; 66: 21-28.
35. Honaramooz A, Li MW, Penedo MC, Meyers S, Dobrinski I. Accelerated maturation of primate testis by xenografting into mice. Biol Reprod 2004; 70: 1500-1503.
36. Honaramooz A, Cui XS, Kim NH, Dobrinski I. Porcine embryos produced after intracytoplasmic sperm injection using xenogeneic pig sperm from neonatal testis tissue grafted in mice. Reprod Fertil Dev 2008; 20: 802-807.
37. Hou M, Andersson M, Zheng C, Sundblad A, Soer O, Jahnukainen K. Decontamination of leukemic cells and enrichment of germ cells from testicular samples with Roser's T-cell leukemia by flow cytometric sorting. Reproduction 2007a; 134: 767-779.
38. Hou M, Andersson M, Eksborg S, Soer O, Jahnukainen K. Xenotransplantation of testicular tissue into nude mice can be used for detecting leukemic cell contamination. Hum Reprod 2007b; 22: 1899-1906.
39. Iwanami Y, Kobayashi T, Kato M, Hirabayashi M, Hochi S. Characteistics of rat round spermatids differentiated from spermatogonial cells during co-culture with Sertoli cells, assessed by flow cytometry, microinsemination and RT-PCR. Theriogenology 2006; 65: 288-298.
40. Izadyar F, Matthijs-Rijsenbilt JJ, Den Ouden K, Creemers LB, Woelders H, de Rooij DG. Development of a cryropreservation protocol for type A spermatogonia. J Androl 2002; 23: 537-545.
41. Jahnukainen K, Hou M, Petersen C, Setchell B, Soer O. Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. Cancer Res 2001; 61: 706-710.
42. Jahnukainen K, Ehmcke J, Hergenrother SD, Schlatt S. Effect of cold storage and cryopreservation of immature non-human primate testicular tissue an spermatogonia stem cell potential in xenografts. Hum Reprod 2007; 22: 1060-1070.
43. Jahnukainen K, Ehmcke J, Hou M, Schlatt S. Testicular function and fertility preservation in male cancer patients. Best Pract Res Clin Endocrinol Metab 2011a; 25: 287-302.
44. Jahnukainen K, Heikkinen R, Henriksson M, Cooper TC, Puukko-Viertomies LR, Maitie O. Semen quality and fertility in adult long-term survivors of childhood acute lymphoblastic leukemia. Fertil Steril 2011b; 96: 837-842.
45. Jahnukainen K, Ehmcke J, Nurmio M, Schlatt S. Autologous ectopic grafting of cryopreserved testicular tissue preserves the fertility of prepubescent monkeys which receive a sterilizing cytotoxic therapy. Cancer Res 2012; 72: 5174-5178.
46. Keros V, Rosenlund B, Hultenby K, Aghajanova L, Levkov L, Hovatta O. Optimizing cryopreservation of human testicular tissue: comparison of protocols with glycerol, propanediol and dimethylsulphoxide as cryoprotectants. Hum Reprod 2005; 20: 1676-1687.
47. Keros V, Hultenby K, Borgstro B, Fridstro M, Jahnukainen K, Hovatta O. Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Hum Reprod 2007; 22: 1384-1395.
48. Kim SS, Radford J, Harris M, Varley J, Rutherford AJ, Lieberman B, Shalet S, Gosden R. Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplants. Hum Reprod 2001; 16: 2056-2060.
49. Kubota H, Avarbock MR, Brinster RL. SSCs share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci USA 2003; 100: 6487-6492.
50. Lampe H, Horwich A, Norman A, Nicholls J, Dearnaley DP. Fertility after chemotherapy for testicular germ cell cancers. J Clin Oncol 1997; 15: 239-245.
51. Lee DR, Kaproth MT, Parks JE. In-vitro production of haploid germ cells from fresh or frozen-thawed testicular cells of neonatal bulls. Biol Reprod 2001; 65: 873-878.
52. Luetjens CM, Stukenborg JB, Nieschlag E, Simoni M, Wistuba J. Complete spermatogenesis in orthotopic but not in ectopic transplants of autologously grafted marmoset testicular tissue. Endocrinology 2008; 149: 1736-1747.
53. Lukusa AK, Vermylen C. Use of hydroxyurea from childhood to adult age in sickle cell disease semen analysis. Haematologica 2008; 93: e67.
54. Morena AR, Boitani C, Pesce M, De Felici M, Stefanini M. Isolation of highly purified type A spermatogonia from prepubertal rat testis. J Androl 1996; 17: 708-717.
55. Nagano MC. Homing efficiency and proliferation kinetics of male germ line stem cells following transplantation in mice. Biol Reprod 2003; 69: 701-707.
56. Nakagawa T, Nabeshima Y, Yoshida S. Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. Dev Cell 2007; 12: 195-206.
57. Nakai M, Kaneko H, Somfai T, Maedomari N, Ozawa M, Noguchi J, Ito J, Kashiwazaki N, Kikuchi K. Production of viable piglets for the first time using sperm derived from ectopic testicular xenografts. Reproduction 2010; 139: 331-335.
58. Ning L, Meng J, Goossens E, Lahoutte T, Marichal M, Tournaye H. Spermatogonial stem cell transplantation in isolated human testis: selection of the most efficient injection site and dosage. Fertil. Steril 2012; 98: 1443-1448.
59. Nurmio M, Keros V, Lateenmai P, Salmi T, Kallajoki M, Jahnukainen K. Effect of childhood acute lymphoblastic therapy on spermatogonia populations and future fertility. J Clin Endocrinol Metab 2009; 94: 2119-2122.
60. Oatley JM, de Avila DM, Reeves JJ, Mclean DJ. Spermatogenesis and germ cell transgene expression in xenografted bovine testicular tissue. Biol Reprod 2004; 71: 494-501.
61. Oatley MJ, Kaucher AV, Racicot KE, Oatley JM. Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of SSCs in mice. Biol Reprod 2011; 85: 347-356.
62. Ogawa T, Arehaga JM, Avarbock MR, Brinster RL. Transplantation of testis germinal cells into mouse seminiferous tubules. Int J Dev Biol 1997; 41: 111-122.
63. Ogawa T, Dobrinski I, Brinster RL. Recipient preparation is critical for spermatogonial transplantation in the rat. Tissue Cell 1999; 31: 461-472.
64. Ohta H, Wakayama T. Generation of normal progeny by intracytoplasmic sperm injection following grafting of testicular tissue from cloned mice that died postnatally. Biol Reprod 2005; 73: 390-395.
65. Parreira GG, Ogawa T, Avarbock MR, Franc LR, Brinster RL, Russell LD. Development of germ cell transplants in mice. Biol Reprod 1998; 59: 1360-1370.
66. Phillips BT, Gassei K, Orwig KE. SSC regulation and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 2010; 365: 1663-1678.
67. Rathi R, Honaramooz A, Zeng W, Turner R, Dobrinski I. Germ cell development in quine testis tissue xenografted into mice. Reproduction 2006; 131: 1091-1098.
68. Relander T, Cavallin-Ståhl E, Garwicz S, Olsson AM, Wille M. Gonadal and sexual function in men treated for childhood cancer. Med Pediatr Oncol 2000; 35: 52-63.
69. Riboldi M, Rubio C, Pellicer A, Gil-Salmon M, Simon C. In-vitro production of haploid cells after coculture of CD49f+ with Sertoli cells from testicular sperm extraction in nonobstructive azoospermic patients. Fertil Steril 2012; 98: 580-590.
70. Ryu BY, Orwig KE, Oatley JM, Avarbock MR, Brinster RL. Effects of aging and niche microenvironment on SSC self-renewal. Stem Cells 2006; 24: 1505-1511.
71. Sa R, Cremades N, Malheiro I, Sousa M. Cryopreservation of human testicular diploid germ cell suspensions. Andrologia 2012; 44: 366-372.
72. Sadri-Ardekani H, Mizrak SC, van Daalen SK, Korver CM, Roepers-Gajadien HL, Koruji M, Hovingh S, de Reijke TM, de la Rosette JJ, van der Veen F et al. Propagation of human SSCs in-vitro. JAMA 2009; 302: 2127-2134.
73. Sadri-Ardekani H, Akhondi MA, van der Veen F, Repping S, van Pelt AM. In-vitro propagation of human prepubertal SSCs. JAMA 2011; 305: 2416-2418.
74. Sato T, Katagiri K, Gohbara A, Inoue K, Ogonuki N, Ogura A, Kubota Y, Ogawa T. In-vitro production of functional sperm in cultured neonatal mouse testes. Nature 2011; 471: 504-507.
75. Schlatt S, Rosiepen G, Weinbauer GF, Rolf C, Brook PF, Nieschlag E. Germ cell transfer into rat, bovine, monkey and human testes. Hum Reprod 1999; 14: 144-150.
76. Schlatt S, Kim SS, Gosden R. Spermatogenesis and steroidogenesis in mouse, hamster and monkey testicular tissue after cryopreservation and heterotopic grafting to castrated hosts. Reproduction 2002; 124: 339-346.
77. Schlatt S, Honaramooz A, Boiani M, Scholer HR, Dobrinski I. Progeny from sperm obtained after ectopic grafting of neonatal mouse testes. Biol Reprod 2003; 68: 2331-2335.
78. Schmidt JA, de Avila JM, McLean DJ. Effect of vascular endothelial growth factor and testis culture on spermatogenesis in bovine ectopic testis tissue xenografts. Biol Reprod 2006; 75: 167-175.
79. Seager SW, Halstead LS. Fertility options and success after spinal cord injury. Urol Clin North Am 1993; 20: 543-548.
80. Shinohara T, Brinster RL. Enrichment and transplantation of SSCs. Int J Androl 2000; 23: 89-91.
81. Shinohara T, Inoue K, Ogonuki N, Kanatsu-Shinohara M, Miki H, Nakata K, Kurome M, Nagashima H, Toyokuni S, Kogishi K et al. Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination. Hum Reprod 2002; 17: 3039-3045.
82. Snedaker AK, Honaramooz A, Dobrinski I. A game of cat and mouse. Xenografting of testis tissue from domestic kittens results in complete cat spermatogenesis in a mouse host. J Androl 2004; 25: 926-930.
83. Soleimani R, Heytens R, Oktay K. Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS ONE 2011; 6: e19475.
84. Sousa M, Cremades N, Alves C, Silva J, Barros A. Developmental potential of human spermatogenic cells co-cultured with Sertoli cells. Hum Reprod 2002; 17: 161-172.
85. Staessen C, Coonen E, Van Assche E, Tournaye H, Joris H, Devroey P, Van Steirteghem AC, Liebaers I. Preimplantation diagnosis for X and Y normality in embryos from three Klinefelter patients. Hum Reprod 1996; 11: 1650-1653.
86. Stukenborg JB, Wistuba J, Luetjens CM, Elhija MA, Huleihel M, Lunenfeld E, Gromoll J, Nieschlag E, Schlatt S. Coculture of spermatogonia with somatic cells in a novel three-dimensional soft-agar-culture-system. J Androl 2008; 29: 312-329.
87. Stukenborg JB, Schlatt S, Simoni M, Yeung CH, Elhija MA, Luetjens CM, Huleihel M, Wistuba J. New horizons for in-vitro spermatogenesis? An update on novel three-dimensional culture systems as tools for meiotic and post-meiotic differentiation of testicular germ cells. Mol Hum Reprod 2009; 15: 521-529.
88. Tournaye H, Staessen C, Liebaers I, Van Assche E, Devroey P, Bonduelle M, Van Steirteghem A. Testicular sperm recovery in niugne 47, XXY Klinefelter patients. Hum Reprod 1996; 11: 1644-1649.
89. Van Saen D, Goossens E, De Block G, Tournaye H. Regeneration of spermatogenesis by grafting testicular tissue or injecting testicular cells into the testes of sterile mice: a comparative study. Fertil Steril 2009; 91: 2264-2272.
90. Van Saen D, Goossens E, Bourgain C, Ferster A, Tournaye H. Meiotic activity in orthotopic xenografts derived from human postpubertal testicular tissue. Hum Reprod 2011; 26: 282-293.
91. Van Saen D, Gies I, De Schepper J, Tournaye H, Goossens E. Can pubertel boys with Klinefelter Syndrome benefit from spermatogonial stem cell banking? Hum Reprod 2012; 27: 323-330.
92. Van Saen D, Goossens E, Aerts JC, Haentjens P, Tournaye H. Does apoptosis cause germ cell loss after testicular tissue grafting? RBM Online, Epub ahead of print.
93. Vernaeve V, Staessen C, Verheyen G, Van Steirteghem A, Devroey P, Tournaye H. Can biological or clinical parameters predict testicular sperm recovery in 47,XXY Klinefelter's syndrome. Hum Reprod 2004; 19: 1135-1139.
94. Vogels A, Moerman P, Frijns JP, Bogaert GA. Testicular histology in boys with Prader-Willi syndrome: fertile or infertile? J Urol 2008; 180: 1800-1804.
95. WallaceW, Anderson R, Irvine D. Fertility preservation for young patients with cancer: who is at risk and what can be offered? Lancet Oncol 2005; 6: 209-218.
96. Wikstro AM, Raivio T, Hadziselimovic F, Wikstro S, Tuuri T, Dunkel L. Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion. J Clin Endocrinol Metab 2004; 89: 2263-2270.
97. Wistuba J, Mundry M, Luetjens CM, Schlatt S. Cografting of hamster (Phodopus sungorus) and marmoset (Callithrix jacchus) testicular tissues into nude mice does not overcome blockade of early spermatogenic differentiation in primate grafts. Biol Reprod 2004; 71: 2087-2091.
98. Wyns C, Curaba M, Petit S, Vanabelle B, Laurent P, Wese JF, Donnez J. Management of fertility preservation in prepubertal patients: 5 years' experience at the Catholic University of Louvain. Hum Reprod 2011; 26: 737-747.
99. Yang Y, Honaramooz A. Effects of medium and hypothermic temperatures on preservation of isolated porcine testis cells. Reprod Fertil Dev 2010; 22: 523-532.
100. Yang Y, Steeg J, Honaramooz A. The effects of tissue sample size and media on short-term hypothermic preservation of porcine testis tissue. Cell Tissue Res 2010; 340: 397-406.
101. Zeng W, Avelar GF, Rathi R, Franca LR, Dobrinski I. The length of the spermatogenic cycle is conserved in porcine and ovine testis xenografts. J Androl 2006; 27: 527-533.