Abstract
Transplantation of male germ line stem cells from a fertile donor to the testis of an infertile recipient restores donor-derived spermatogenesis in the recipient testis and the resulting sperm pass the donor genotype to the offspring of the recipient. Germ cell transplantation has been an invaluable tool to elucidate the biology of male germ line stem cells and their niche in the testis, develop systems to isolate and culture spermatogonial stem cells, examine defects in spermatogenesis, correct male infertility and introduce genetic changes into the male germ line. Although most widely studied in rodents, germ cell transplantation has been applied to larger mammals, including primates. Recently, ectopic grafting of testis tissue from diverse donor species, including primates, into a mouse host has opened an additional possibility to study spermatogenesis and to produce fertile sperm from immature donors. Testis xenografts are ideally suitable to study toxicants or drugs with the potential to enhance or suppress male fertility without the necessity of performing experiments in the target species. Therefore, transplantation of germ cells or xenografting of testis tissue represent powerful approaches for the study, preservation, and manipulation of male fertility.
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References
Avarbock MR, Brinster CJ, Brinster RL (1996) Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nature Med 2:693–696
Boettger-Tong HL, Johnston DS, Russell LD, Griswold MD, Bishop CE (2000) Juvenile spermatogonial depletion (jsd) mutant seminiferous tubules are capable of supporting transplanted spermatogenesis Biol Reprod 63:1185–1191
Brinster RL, Avarbock MR (1994) Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci U S A 91:11303–11307
Brinster RL, Zimmermann JW (1994) Spermatogenesis following male germcell transplantation. Proc Natl Acad Sci U S A 91:11298–11302
Brook PF, Radford JA, Shalet SM, Joyce AD, Gosden RG (2001) Isolation of germ cells from human testicular tissue for low temperature storage and autotransplantation. Fertil Steril 75:269–274
Buaas FW, Kirsh AL, Sharma M, McLean DJ, Morris JL, Griswold MD, de Rooij DG, Braun RE (2004) Plzf is required in adult male germ cells for stem cell self-renewal. Nat Genet 36:647–652
Chuma S, Kanatsu-Shinohara M, Inoue K, Ogonuki N, Miki H, Toyokuni S, Hosokawa M, Nakatsuji N, Ogura A, Shinohara T (2005) Spermatogenesis from epiblast and primordial germ cells following transplantation into postnatal mouse testis. Development: 132:117–122
Clermont Y (1972) Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 52:198–236
Clouthier DE, Avarbock MR, Maika SD, Hammer RE, Brinster RL (1996) Rat spermatogenesis in mouse testis. Nature 381:418–421
Costoya JA, Hobbs RM, Barna M, Cattoretti G, Manova K, Sukhwani M, Orwig KE, Wolgemuth DJ, Pandolfi PP (2004) Essential role of Plzf in maintenance of spermatogonial stem cells. Nat Genet 36:653–659
Creemers LB, Meng X, den Ouden K, van Pelt MM, Izadyar F, Santoro M, de Rooij DG, Sariola H (2002) Transplantation of germ cells from glial cell line-derived neurotrophic factor-overexpressing mice to host testes depleted of endogenous spermatogenesis by fractionated irradiation. Biol Reprod 66:1579–1584
Dobrinski I, Avarbock MR, Brinster RL (1999a) Transplantation of germ cells from rabbits and dogs into mouse testes. Biol Reprod 61:1331–1339
Dobrinski I, Ogawa T, Avarbock MR, Brinster RL (1999b) Computer-assisted image analysis to assess colonization of recipient seminiferous tubules by spermatogonial stem cells from transgenic donor mice. Mol Reprod Dev 53:142–148
Dobrinski I, Avarbock MR, Brinster RL (2000) Germ cell transplantation from large domestic animals into mouse testes. Mol Reprod Develop 57:270–279
Dobrinski I, Ogawa T, Avarbock MR, Brinster RL (2001) Effect of the GnRH-agonist leuprolide on colonization of recipient testes by donor spermatogonial stem cells after transplantation in mice. Tissue Cell 33:200–207
Dyce PW, Zhu H, Craig J, Li J (2004) Stem cells with multilineage potential derived from porcine skin. Biochem Biophys Res Com 316:651–658
Feng L-X, Chen Y, Dettin L, Reijo Pera RA, Herr JC, Goldberg E, Dym M (2002) Generation and in vitro differentiation of a spermatogonial cell line. Science 297:392–395
Fujita K, Ohta H, Tsujimura A, Takao T, Miyagawa Y, Takada S, Matsumiya K, Wakayama T, Okuyama A (2005) Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia. J Clin Invest 115:1855–1861
Franca LR, Ogawa T, Avarbock MR, Brinster RL, Russell LD (1998) Germ cell genotype controls cell cycle during spermatogenesis in the rat. Biol Reprod 59:1371–1377
Goossens E, Frederickx V, De Block G, Van Steirteghem A, Tournaye H (2003) Reproductive capacity of sperm obtained after germ cell transplantation in a mouse model. Hum Reprod 18:1874–1880
Hamra FK, Gatlin J, Chapman KM, Grellhesl DM, Garcia JV, Hammer RE, Garbers DL (2002) Production of transgenic rats by lentiviral transduction of male germ-line stem cells. Proc Natl Acad Sci U S A 99:14931–14936
Hamra FK, Schultz N, Chapman KM, Grellhesl DM, Cronkhite JT, Hammer RE, Garbers DL (2004) Defining the spermatogonial stem cell. Dev Biol 269:393–410
Hofmann M-C, Braydich-Stolle L, Dettin L, Johnson E, Dym M (2005) Immortalization of mouse germ line stem cells. Stem Cells 23:200–210
Honaramooz A, Megee SO, Dobrinski I (2002a) Germ cell transplantation in pigs. Biol Reprod 60:21–28
Honaramooz A, Snedaker A, Boiani M, Scholer HR, Dobrinski I, Schlatt S (2002b) Sperm from neonatal mammalian testes grafted in mice. Nature 418:778–781
Honaramooz A, Behboodi E, Blash, S, Megee SO, Dobrinski I (2003a) Germ cell transplantation in goats. Mol Reprod Dev 64:422–428
Honaramooz A, Behboodi E, Megee SO, Overton SA, Galantino-Homer HL, Echelard Y, Dobrinski I (2003b) Fertility and germline transmission of donor haplotype following germ cell transplantation in immunocompetent goats. Biol Reprod 69:1260–1264
Honaramooz A, Li M-W, Penedo MCT, Meyers SA, Dobrinski I (2004) Accelerated maturation of primate testis by xenografting into mice. Biol Reprod 70:1500–1503
Huckins C (1971) The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation, and maturation. Anat Rec 160:533–558
Izadyar F, den Ouden K, Stout TAE, Stout J, Coret J, Lankveld DPK, Spoormakers TJP, Colenbrander B, Oldenbroek JK, Van der Ploeg KD, Woelders H, Kal HB, de Rooij DG (2003) Autologous and homologous transplantation of bovine spermatogonial stem cells. Reproduction 126:765–774
Izadyar F, Matthijs-Rijsenbilt JJ, den Ouden K, Creemers LB, Woelders H, de Rooij D (2002). Development of a cryopreservation protocol for type A spermatogonia. J Androl 23:537–545
Jahnukainen K, Hou M, Petersen C, Setchell B, Soder O (2001) Intratesticular transplantation of testicular cells from leukemic rats causes transmission of leukemia. Cancer Res 61:706–710
Jeong D, McLean DJ, Griswold MD (2003) Long-term culture and transplantation of murine testicular germ cells. J Androl 24:661–669
Jiang FX, Short RV (1995) Male germ cell transplantation in rats: apparent synchronization of spermatogenesis between host and donor seminiferous epithelia. Int J Androl 18:326–330
Johnston DS, Russell LD, Friel PJ, Griswold MD (2001) Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation. Endocrinology 142:2405–2408
Kanatsu-Shinohara M, Ogonuki N, Inoue K, Ogura A, Toyokuni S, Honjo T, Shinohara T (2003a) Allogeneic offspring produced by male germ line stem cell transplantation into infertile mouse testis. Biol Reprod 68:167–173
Kanatsu-Shinohara M, Ogonuki N, Inoue K, Miki H, Ogura A, Toyokuni S, Shinohara T (2003b) Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol Reprod 69:612–616
Kanatsu-Shinohara M, Toyokuni S, Morimoto T, Matsui S, Honjo T, Shinohara T (2003c) Functional assessment of self-renewal activity of male germline stem cells following cytotoxic damage and serial transplantation. Biol Reprod 68:1801–1807
Kanatsu-Shinohara M, Toyokuni S, Shinohara T (2004a) CD9 is a surface marker on mouse and rat male germline stem cells. Biol Reprod 70:70–75
Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T (2004b) Generation of pluripotent stem cells from neonatal mouse testis. Cell 119:1001–1012
Kanatsu-Shinohara M, Miki H, Inoue K, Ogonuki N, Toyokuni S, Ogura A, Shinohara T (2005) Long-term culture of mouse male germline stem cells under serum-or feeder-free conditions. Biol Reprod 72:985–991
Kubota H, Avarbock MR, Brinster RL (2003) Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci U S A 100:6487–6492
Kubota H, Avarbock MR, Brinster RL (2004) Culture conditions and single growth factors affect fate determination of mouse spermatogonial stem cells. Biol Reprod 71:722–731
Kues WA, Petersen B, Mysegades W, Carnwath JW, Niemann H (2005) Isolation of murine and porcine fetal stem cells from somatic tissue. Biol Reprod 72:1020–1028
Lassalle B, Bastos H, Louis JP, Testart J, Dutrillaux B, Fouchet P, Allemand I (2004) ’side population’ cells in adult mouse testis express Bcrp1 gene and are enriched in spermatogonia and germinal stem cells. Development 131:479–487
Mahato D, Goulding EH, Korach KS, Eddy EM (2000) Spermatogenic cells do not require estrogen receptor-α for development of function. Endocrinology 141:1273–1276
Meistrich ML, van Beek MEAB (1993) Spermatogonial stem cells. In: Desjardins C, Ewing LL (eds) Cell and molecular biology of testis. Oxford University Press, Oxford, pp 266–295
Nagano M (2003) Homing efficiency and proliferation kinetics of male germ line stem cells following transplantation in mice. Biol Reprod 69:701–707
Nagano M, Avarbock MR, Leonida EB, Brinster CJ, Brinster RL (1998) Culture of mouse spermatogonial stem cells. Tissue Cell 30:389–397
Nagano M, Avarbock MR, Brinster RL (1999) Pattern and kinetics of mouse donor spermatogonial stem cell colonization in recipient testes. Biol Reprod 60:1429–1436
Nagano M, Brinster CJ, Orwig KE, Ryu B-Y, Avarbock MR, Brinster RL (2001a) Transgenic mice produced by retroviral transduction of male germ-line stem cells. Proc Natl Acad Sci U S A 98:13090–13095
Nagano M, McCarrey JR, Brinster RL (2001b) Primate spermatogonial stem cells colonize mouse testes. Biol Reprod 64:1409–1416
Nagano M, Patrizio P, Brinster RL (2002a) Long-term survival of human spermatogonial stem cells in mouse testes. Fertil Steril 78:1225–1233
Nagano M, Watson DJ, Ryu B-Y, Wolfe JH, Brinster RL (2002b) Lentiviral vector transduction of male germ line stem cells in mice. FEBS Lett 524:111–115
Nagano M, Ryu B-Y, Brinster CJ, Avarbock MR, Brinster RL (2003) Maintenance of mouse male germ line stem cells in vitro. Biol Reprod 68:2207–2214
Noguchi J, Toyama Y, Yuasa S, Kikuchi K, Kaneko M (2002) Hereditary defects in both germ cells and the blood-testis barrier system in as-mutant rats: evidence from spermatogonial transplantation and tracer permeability analysis. Biol Reprod 67:880–888
Ogawa T, Arechaga JM, Avarbock MR, Brinster RL (1997) Transplantation of testis germinal cells into mouse seminiferous tubules. Int J Dev Biol 41:111–122
Ogawa T, Dobrinski I, Avarbock MR, Brinster RL (1998) Leuprolide, a gonadotropin releasing hormone agonist, enhances colonization after spermatogonial transplantation into mouse testes. Tissue Cell 30:583–588
Ogawa T, Dobrinski I, Avarbock MR, Brinster RL (1999a) Xenogeneic spermatogenesis following transplantation of hamster germ cells to mouse testes. Biol Reprod 60:515–521
Ogawa T, Dobrinski I, Brinster RL (1999b) Recipient preparation is critical for spermatogonial transplantation in the rat. Tissue Cell 31:461–472
Ogawa T, Dobrinski I, Avarbock MR, Brinster RL (2000) Transplantation of male germ line stem cells restores fertility in infertile mice. Nature Med 6:29–34
Ogawa T, Ohmura M, Yumura Y, Sawada H, Kubota Y (2003) Expansion of murine spermatogonial stem cells through serial transplantation. Biol Reprod 68:316–322
Ohta H, Yomogida K, Dohmae K, Nishimune Y (2000) Regulation of proliferation and differentiation in spermatogonial stem cells: the role of c-kit and its ligand SCF. Development 127:2125–2131
Ohta H, Yomogida K, Tadokoro Y, Tohda A, Dohmae K, Nishimune Y (2001) Defect in germ cells, not supporting cells, is the cause of male infertility in the jsd mutant mouse: proliferation of spermatogonial stem cells without differentiation. Int J Androl 24:15–23
Orwig KE, Avarbock MR, Brinster RL (2002a) Retrovirus-mediated modification of male germline stem cells in rats. Biol Reprod 67:874–879
Orwig KE, Ryu B-Y, Avarbock MR, Brinster RL (2002b) Male germ-line stem cell potential is predicted by morphology of cells in neonatal rat testes. Proc Natl Acad Sci U S A 99:11706–11711
Parreira GC, Ogawa T, Avarbock MR, Franca LR, Brinster RL, Russell LD (1998) Development of germ cell transplants in mice. Biol Reprod 59:1360–1370
Radford J (2003) Restoration of fertility after treatment for cancer. Horm Res 59:21–23
Radford JA, Shalet SM, Lieberman BA (1999). Fertility after treatment for cancer. BMJ 319:935–936
Reis MM, Tsai MC, Schlegel PN, Feliciano M, Raffaelli R, Rosenwaks Z, Palermo GD (2000) Xenogeneic transplantation of human spermatogonia. Zygote 8:97–105
Rilianawati, Speed R, Taggart M, Cooke HJ (2003) Spermatogenesis in testes of Dazl null mice after transplantation of wild-type germ cells. Reproduction 126:599–604
Russell LD, Brinster RL (1996) Ultrastructural observations of spermatogenesis following transplantation of rat testis cells into mouse seminiferous tubules. J Androl 17:615–627
Russell LD, Ettlin RA, SinhaHikim AP, Clegg ED (1990) Mammalian spermatogenesis. In: Russell LD, Ettlin RA, SinhaHikim AP, Clegg ED (eds) Histological and histopathological evaluation of the testis. Cache River Press, Clearwater, pp 1–40
Ryu B-Y, Orwig KE, Avarbock MR, Brinster RL (2003) Stem cell and niche development in the postnatal rat testis. Dev Biol 263: 253–263
Ryu B-Y, Orwig KE, Kubota H, Avarbock MR, Brinster RL (2004) Phenotypic and functional characteristics of spermatogonial stem cells in rats. Dev Biol 274:158–170
Schlatt S, Foppiani L, Rolf C, Weinbauer GF, Nieschlag E (2002a) Germ cell transplantation into X-irradiated monkey testes. Hum Reprod 17:55–62
Schlatt S, Kim SS, Gosden R (2002b) Spermatogenesis and steroidogenesis in mouse, hamster and monkey testicular tissue after cryopreservation and heterotopic grafting to castrated hosts. Reproduction 124:339–346
Schlatt S, Honaramooz A, Boiani M, Scholer HR, Dobrinski I (2003) Progeny from sperm obtained after ectopic grafting of neonatal mouse testes. Biol Reprod 68:2331–2335
Shinohara T, Avarbock MR, Brinster RL (1999) β1-and α6-integrin are surface markers on mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 96:5504–5509
Shinohara T, Avarbock MR, Brinster RL (2000a) Functional analysis of spermatogonial stem cells in Steel and cryptorchid infertile mouse models. Dev Biol 220:401–411
Shinohara T, Orwig KE, Avarbock MR, Brinster RL (2000b) Spermatogonial stem cell enrichment by multiparameter selection of mouse testis cells. Proc Natl Acad Sci U S A 97:8346–8351
Shinohara T, Orwig KE, Avarbock MR, Brinster RL (2001) Remodeling of the postnatal mouse testis is accompanied by dramatic changes in stem cell number and niche accessibility. Proc Natl Acad Sci U S A 98:6186–6191
Shinohara T, Inoue K, Ogonuki N, Kanatsu-Shinohara M, Miki H, Nakata K, Kurome M, Nagashima H, Toyokuni S, Kogishi K, Honjo T, Ogura A (2002) Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination. Hum Reprod 17:3039–3045
Shinohara T, Orwig KE, Avarbock MR, Brinster RL (2003) Restoration of spermatogenesis in infertile mice by Sertoli cell transplantation. Biol Reprod 68:1064–1071
Tegelenbosch RAJ, de Rooij DG (1993) A quantitative study of spermatogonial multiplication and stem cell renewal in the C3H/101 F1 hybrid mouse. Mut Res 290:193–200
Van Pelt MM, Roepers-Gajadien HL, Gademan IS, Creemers LB, de Rooij DG, van Dissel-Emiliani FMF (2002) Establishment of cell lines with rat spermatogonial stem cell characteristics. Endocrinology 143:1845–1850
Ventela S, Ohta H, Parvinen M, Nishimune Y (2002) Development of stages of the cycle in mouse seminiferous epithelium after transplantation of green fluorescent protein-labeled spermatogonial stem cells. Biol Reprod 66:1422–1429
Wistuba J, Schlatt S, Cantauw C, von Schonfeldt V, Nieschlag E, Behr R (2002) Transplantation of wild-type spermatogonia leads to complete spermatogenesis in testes of cyclic 3′,5′-adenosine monophosphate response element modulator-deficient mice. Biol Reprod 67:1052–1057
Yomogida K, Yagura Y, Tadokoro Y, Nishimune Y (2003) Dramatic expansion of germinal stem cells by ectopically expressed human glial cell line-derived neurotrophic factor in mouse Sertoli cells. Biol Reprod 69:1303–1307
Zhang Z, Renfree MB, Short RV (2003) Successful intra-and interspecific male germ cell transplantation in the rat. Biol Reprod 68:961–967
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Dobrinski, I. (2006). Transplantation of Germ Line Stem Cells for the Study and Manipulation of Spermatogenesis. In: Morser, J., Nishikawa, S.I., Schöler, H.R. (eds) Stem Cells in Reproduction and in the Brain. Ernst Schering Research Foundation Workshop, vol 60. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-31437-7_12
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