Review: Male germ line stem cells: from cell biology to cell therapy?
David Pei-Cheng Lin A B , Ming-Yu Chang C , Bo-Yie Chen B and Han-Hsin Chang D E
+ Author Affiliations
- Author Affiliations
A School of Medical Technology, Chung Shan Medical University, Taichung City, Taiwan, ROC.
B Institute of Biochemistry, Chung Shan Medical University, Taichung City, Taiwan, ROC.
C Institute of Medical Research, Chung Shan Medical University, Taichung City, Taiwan, ROC.
D School of Nutrition, Chung Shan Medical University, Taichung City, Taiwan, ROC.
E To whom correspondence should be addressed. email: jhhc@csmu.edu.tw
Reproduction, Fertility and Development 15(6) 323-331 https://doi.org/10.1071/RD03046
Submitted: 10 July 2003 Accepted: 12 November 2003 Published: 12 November 2003
Abstract
Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.
Extra keywords: germ line stem cell transplantation
Acknowledgments
The authors’ work reported herein was supported financially by an intramural grant CSMU-88-OM-B-031 to H.-H.C. The authors thank Professor Matthew H. Kaufman (University of Edinburgh) for his assistance in the revision of the manuscript.
References
Avarbock, M. R. , Brinster, C. J. , and Brinster, R. L. (1996). Reconstitution of spermatogenesis from frozen spermatogonial stem cells. Nat. Med. 2, 693–696.
| PubMed |
Beck, A. R. , Miller, I. J. , Anderson, P. , and Streuli, M. (1998). RNA-binding protein TIAR is essential for primordial germ cell development. Proc. Natl Acad. Sci. USA 95, 2331–2336.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Beddington, R. S. , and Robertson, E. J. (1999). Axis development and asymmetry in mammals. Cell 96, 195–209.
| PubMed |
Besmer, P. , Manova, K. , Duttlinger, R. , Huang, E. J. , Packer, A. , Gyssler, C. , and Bachvarova, R. F. (1993). The kit-ligand (steel factor) and its receptor c-kit/W: pleiotropic roles in gametogenesis and melanogenesis. Development 119S, 125–137.
Brinster, R. L. , and Avarbock, M. R. (1994). Germline transmission of donor haplotype following spermatogonial transplantation. Proc. Natl Acad. Sci. USA 91, 11 303–11 307.
Brinster, R. L. , and Zimmermann, J. W. (1994). Spermatogenesis following male germ-cell transplantation. Proc. Natl Acad. Sci. USA 91, 11 289–11 302.
Buehr, M. , McLaren, A. , Bartley, A. , and Darling, S. (1993). Proliferation and migration of primordial germ cells in We/We mouse embryos. Dev. Dyn. 198, 182–189.
| PubMed |
Chang, H. , and Matzuk, M. M. (2001). Smad5 is required for mouse primordial germ cell development. Mech. Dev. 104, 61–67.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Chiquoine, A. D. (1954). The identification, origin, and migration of primordial germ cells in the mouse. Anat. Rec. 118, 135–146.
| PubMed |
Clouthier, D. E. , Avarbock, M. R. , Maika, S. D. , Hammer, R. E. , and Brinster, R. L. (1996). Rat spermatogenesis in mouse testis. Nature 381, 418–421.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Cooke, J. E. , Heasman, J. , and Wylie, C. C. (1996). The role of interleukin-4 in the regulation of mouse primordial germ cell numbers. Dev. Biol. 174, 14–21.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
De Felici, M. , and Dolci, S. (1991). Leukemia inhibitory factor sustains the survival of mouse primordial germ cell cultured on TM4 feeder layer. Dev. Biol. 147, 281–284.
| PubMed |
de Kretser, D. M. (1990). Morphology and physiology of the testis In
de Kretser, D. M. , McLachlan, R. I. , Robertson, D. M. , and Wreford, N. G. (1992). Control of spermatogenesis by follicle stimulating hormone and testosterone. Baillieres Clin. Endocrinol. Metab. 6, 335–354.
| PubMed |
de Rooji, D. G. , and Russell, L. D. (2000). All you wanted to know about spermatogonia but were afraid to ask. J. Androl. 21, 776–798.
| PubMed |
Dobrinski, I. , Avarbock, M. R. , and Brinster, R. L. (1999). Transplantation of germ cells from rabbits and dogs into mouse testes. Biol. Reprod. 61, 1331–1339.
| PubMed |
Dobrinski, I. , Avarbock, M. R. , and Brinster, R. L. (2000). Germ cell transplantation from large domestic animals into mouse testes. Mol. Reprod. Dev. 57, 270–279.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Dobrinski, I. , Ogawa, T. , Avarbock, M. R. , and Brinster, R. L. (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.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Dolci, S. , Williams, D. E. , Ernst, M. K. , Resnick, J. L. , Brannan, C. I. , Lock, L. F. , Lyman, S. D. , Boswell, H. S. , and Donovan, P. J. (1991). Requirement for mast cell growth factor for primordial germ cell survival in culture. Nature 352, 809–811.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Dominguez, F. , Pellicer, A. , and Simon, C. (2002). Paracrine dialogue in implantation. Mol. Cell. Endocrinol. 186, 175–181.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Donovan, P. J. , Stott, D. , Cairns, L. A. , Heasman, J. , and Wylie, C. C. (1986). Migratory and postmigratory mouse primordial germ cells behave differently in culture. Cell 44, 831–838.
| PubMed |
Feng, L.-X. , Chen, Y. , Dettin, L. , Reijo-Pera, R. A. , Herr, J. C. , Goldberg, E. , and Dym, M. (2002). Generation and in vitro differentiation of a spermatogonia cell line. Science 297, 392–395.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Forbes, S. , Vig, P. , Poulsom, R. , Thomas, H. , and Alison, M. (2002). Hepatic stem cells. J. Pathol. 197, 510–518.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Gage, F. H. (2000). Mammalian neural stem cells. Science 287, 1433–1438.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Gerstenfeld, L. C. , Cullinance, D. M. , Barnes, G. L. , Graves, D. T. , and Einhorn, T. A. (2003). Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J. Cell. Biochem. 88, 873–884.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ginsburg, M. , Snow, M. H. , and McLaren, A. (1990). Primordial germ cell in the mouse embryo during gastrulation. Development 110, 521–528.
| PubMed |
Godin, I. , and Wylie, C. C. (1991). TGF-β1 inhibits proliferation and has a chemotropic effect on mouse primordial germ cells in culture. Development 113, 1451–1457.
| PubMed |
Hamra, F. K. , Gatlin, J. , Chapman, K. M. , Grellhels, D. M. , Garcia, J. V. , Hammer, R. E. , and Garbers, D. L. (2002). Production of transgenic rats by lentiviral transduction of male germ-line stem cells. Proc. Natl Acad. Sci. USA 99, 14 931–14 936.
| Crossref | GoogleScholarGoogle Scholar |
Heller, C. G. , and Clermont, Y. (1963). Spermatogenesis in man: an estimate of its duration. Science 140, 184–186.
| PubMed |
Hofmann, M. C. , Narisawa, S. , Hess, R. A. , and Millan, J. L. (1992). Immortalization of germ cells and somatic testicular cells using the SV40 large T antigen. Exp. Cell Res. 201, 417–435.
| PubMed |
Hofmann, M. C. , Hess, R. A. , Goldberg, E. , and Millan, J. L. (1994). Immortalized germ cells undergo meiosis in vitro. Proc. Natl Acad. Sci. USA 91, 5533–5537.
| PubMed |
Honaramooz, A. , Megee, S. O. , and Dobrinski, I. (2002). Germ cell transplantation in pigs. Biol. Reprod. 66, 21–28.
| PubMed |
Honaramooz, A. , Behboodi, E. , Blash, S. , Megee, S. O. , and Dobrinski, I. (2003). Germ cell transplantation in goats. Mol. Reprod. Dev. 64, 422–428.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Houston, D. W. , and King, M. L. (2000). Germplasm and molecular determinants of germ cell fate. Curr. Top. Dev. Biol. 50, 155–181.
| PubMed |
Ikawa, M. , Tergaokar, V. , Ogura, A. , Ogonuki, N. , Inoue, K. , and Verma, I. M. (2002). Restoration of spermatogenesis by lentiviral gene transfer: offspring from infertile mice. Proc. Natl Acad. Sci. USA 99, 7524–7529.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ikenishi, K. , and Tanaka, T. S. (2000). Spatio-temporal expression of Xenopus vasa homolog, XVLG1, in oocytes and embryos: the presence of XVLG1 RNA in somatic cells as well as germline cells. Dev. Growth Differ. 42, 95–103.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Izadyar, F. , Denouden, K. , Creemers, L. B. , Posthuma, G. , Parvinen, M. , and De Rooij, D. G. (2003). Proliferation and differentiation of bovine type a spermatogonia during long-term culture. Biol. Reprod. 68, 272–281.
| PubMed |
Johnston, D. S. , Russell, L. D. , Friel, P. J. , and Griswold, M. D. (2001). Murine germ cells do not require functional androgen receptors to complete spermatogenesis following spermatogonial stem cell transplantation. Endocrinology 142, 2405–2408.
| PubMed |
Kawase, E. , Yamamoto, H. , Hashimoto, K. , and Nakatsuji, N. (1994). Tumor necrosis factor-α (TNF-α) stimulates proliferation of mouse primordial germ cells in culture. Dev. Biol. 161, 91–95.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Kierszenbaum, A. L. (2002). Genomic imprinting and epigenetic reprogramming: unearthing the garden of forking paths. Mol. Reprod. Dev. 63, 269–272.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Koshimizu, U. , Watanabe, M. , and Nakatsuji, N. (1995). Retinoic acid is a potent growth activator of mouse primordial germ cells in vitro. Dev. Biol. 168, 683–685.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Lawson, K. A. , and Hage, W. J. (1994). Clonal analysis of the origin of primordial germ cells in the mouse Ciba Found. Symp. 182, 68–84.
| PubMed |
Lawson, K. A. , Dunn, N. R. , Roelen, B. A. , Zeinstra, L. M. , Davis, A. M. , Wright, C. V. , Korving, J. P. , and Hogan, B. L. M. (1999). Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev. 13, 424–436.
| PubMed |
Mahato, D. , Goulding, E. H. , Korach, K. S. , and Eddy, E. M. (2000). Spermatogenic cells do not require estrogen receptor-alpha for development or function. Endocrinology 141, 1273–1276.
| PubMed |
Marshman, E. , Booth, C. , and Potten, C. S. (2002). The intestinal epithelial stem cell. Bioessay 24, 91–98.
| Crossref | GoogleScholarGoogle Scholar |
Matsubara, N. , Takahashi, Y. , Nishina, Y. , Mukouyama, Y. , and Yanagisawa, M. , et al. (1996). A receptor tyrosine kinase, Sky, and its ligand Gas6 are expressed in gonads and support primordial germ cell growth or survival in culture. Dev. Biol. 180, 499–510.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Matsui, Y. , Toksoz, D. , Nishikawa, S. , Williams, D. , Zsebo, K. , and Hogan, B. L. M. (1991). Effect of Steel factor and leukemia inhibitory factor on murine primordial germ cells in culture. Nature 353, 750–752.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Matsui, Y. , Zsebo, K. , and Hogan, B. L. M. (1992). Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell 70, 841–847.
| PubMed |
Matsumoto, A. M. (1995). Infertility: evaluation and treatment. In
Matsumoto, A. M. , and Bremmer, W. J. (1987). Endocrinology of the hypothalamic–pituitary–testicular axis with particular reference to the hormonal control of spermatogenesis. Baillieres Clin. Endocrinol. Metab. 1, 71–87.
| PubMed |
Mayani, H. (2003). A glance into somatic stem cell biology: basic principles, new concepts, and clinical relevance. Arch. Med. Res. 34, 3–15.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Mintz, B. B. , and Russell, E. S. (1957). Gene-induced embryological modification of primordial germ cell in mouse. J. Exp. Zool. 30, 97–118.
Nagano, M. , and Brinster, R. L. (1998). Spermatogonial transplantation and reconstitution of donor cell spermatogenesis in recipient males. APMIS 106, 47–55.
| PubMed |
Nagano, M. , Brinster, C. J. , Orwig, K. E. , Ryu, B.-Y. , Avarbock, M. R. , and Brinster, R. L. (2001). Transgenic mice produced by retroviral transduction of male germ-line stem cells. Proc. Natl Acad. Sci. USA 98, 13 090–13 095.
| Crossref | GoogleScholarGoogle Scholar |
Nagano, M. , Patrizio, P. , and Brinster, R. L. (2002). Long-term survival of human spermatogonial stem cells in mouse testes. Fertil. Steril. 78, 1225–1233.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Oatley, J. M. , de Avila, D. M. , McLean, D. J. , Griswold, M. D. , and Reeves, J. J. (2002). Transplantation of bovine germinal cells into mouse testes. J. Anim. Sci. 80, 1925–1931.
| PubMed |
Obata, Y. , Kono, T. , and Hatada, I. (2002). Maturation of mouse fetal germ cells in vitro. Nature 418, 497–498.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ogawa, T. (2001). Spermatogonial transplantation: the principle and possible applications. J. Mol. Med. 79, 368–374.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ogawa, T. , Dobrinski, I. , Avarbock, M. R. , and Brinster, R. L. (1998). Leuprolide, a gonadotropin-releasing hormone agonist, enhances colonization after spermatogonial transplantation into mouse testes. Tissue Cell 30, 583–588.
| PubMed |
Ogawa, T. , Dobrinski, I. , and Brinster, R. L. (1999a). Recipient preparation is critical for spermatogonial transplantation in the rat. Tissue Cell 31, 461–472.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ogawa, T. , Dobrinski, I. , Avarbock, M. R. , and Brinster, R. L. (1999b). Xenogeneic spermatogenesis following transplantation of hamster germ cells to mouse testes. Biol. Reprod. 60, 515–521.
| PubMed |
Ogawa, T. , Dobrinski, I. , Avarbock, M. R. , and Brinster, R. L. (2000). Transplantation of male germ line stem cells restores fertility in infertile mice. Nat. Med. 6, 29–34.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Ohta, H. , Yomogida, K. , Tadokoro, Y. , Tohda, A. , Dohmae, K. , and Nishimune, Y. (2001). Defect in germ cells, not in 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.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Orwig, K. E. , Avarbock, M. R. , and Brinster, R. L. (2002). Retrovirus-mediated modification of male germline stem cells in rats. Biol. Reprod. 67, 874–879.
| PubMed |
Parreira, G. G. , Ogawa, T. , Avarbock, M. R. , França, L. R. , Brinster, R. L. , and Russell, L. D. (1998). Development of germ cell transplants in mice. Biol. Reprod. 59, 1360–1370.
| PubMed |
Parreira, G. G. , Ogawa, T. , Avarbock, M. R. , França, L. R. , Hausler, C. L. , Brinster, R. L. , and Russell, L. D. (1999). Development of germ cell transplants: morphometric and ultrastructural studies. Tissue Cell 31, 242–254.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Pesce, M. , Canipari, R. , Ferri, G. L. , Siracusa, G. , and De Felici, M. (1996). Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates adenylate cyclase and promotes proliferation of mouse primordial germ cells. Development 122, 215–221.
| PubMed |
Pesche, M. , Gioiaklinger, F. , and De Felici, M. (2002). Derivation in culture of primordial germ cells from cells of the mouse epiblast: phenotypic induction and growth control by Bmp4 signaling. Mech. Dev. 112, 15–24.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Rassoulzadegan, M. (2002). Conquering the male germ line. Nat. Genet. 30, 133–134.
| PubMed |
Resnick, J. L. , Bixler, L. S. , Cheng, L. , and Donovan, P. J. (1992). Long-term proliferation of mouse primordial germ cells in culture. Nature 359, 550–551.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Resnick, J. L. , Ortiz, M. , Keller, J. R. , and Donovan, P. (1998). Role of fibroblast growth factors and their receptors in mouse primordial germ cell growth. Biol. Reprod. 59, 1224–1229.
| PubMed |
Rothman, C. M. , Sims, C. A. , and Stotts, C. L. (1982). Sertoli cell only syndrome. Fertil. Steril. 38, 388–390.
| PubMed |
Sakurai, T. , Iguchi, T. , Moriwaki, K. , and Noguchi, M. (1995). The ter mutation first causes primordial germ cell deficiency in ter/ter mouse embryos at 8 days of gestation. Dev. Growth Differ. 37, 293–302.
| Crossref | GoogleScholarGoogle Scholar |
Schlatt, S. , Foippiani, L. , Rolf, C. , Weinbauer, G. F. , and Nieschlag, E. (2002). Germ cell transplantation into X-irradiated monkey testes. Hum. Reprod. 17, 55–62.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Shinohara, T. , Orwig, K. E. , Avarbock, M. R. , and Brinster, R. L. (2002). Germ line stem cell competition in postnatal mouse testes. Biol. Reprod. 66, 1491–1497.
| PubMed |
Slack, J. M. W. (2000). Stem cells in epithelial tissues. Science 287, 1431–1433.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Snow, M. , Cox, S.-L. , Jenkin, G. , Trounson, A. , and Shaw, J. (2002). Generation of live young from xenografted mouse ovaries. Science 297, 2227.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Takabayashi, S. , Sasaoka, Y. , Yamashita, M. , Tokumoto, T. , Ishikawa, K. , and Noguchi, M. (2001). Novel growth factor supporting survival of murine primordial germ cells: evidence from conditional medium of ter fetal gonadal somatic cells. Mol. Reprod. Dev. 60, 384–396.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Tam, P. P. , and Snow, M. H. L. (1981). Proliferation and migration of primordial germ cells during compensatory growth in mouse embryos. J. Embryol. Exp. Morph. 64, 133–147.
| PubMed |
Tanaka, S. S. , and Matsui, Y. (2002). Developmentally regulated expression of mil-1 and mil-2, mouse interferon-induced transmembrane protein like genes, during formation and differentiation of primordial germ cells. Gene Express. Patterns 2, 297–303.
| Crossref | GoogleScholarGoogle Scholar |
Tascou, S. , Nayernia, K. , Samani, A. , Schmidtke, J. , Vogel, T. , Engel, W. , and Burfeind, P. (2000). Immortalization of murine male germ cells at a discrete stage of differentiation by a novel directed promoter-based selection strategy. Biol. Reprod. 63, 1555–1561.
| PubMed |
Toyoda-Ohno, H. , Obinata, M. , and Matsui, Y. (1999). Members of the ErbB receptor tyrosine kinases are involved in germ cell development in fetal mouse gonads. Dev. Biol. 215, 399–406.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Tremblay, J. D. , Dunn, N. R. , and Robertson, E. J. (2001). Mouse embryos lacking Smad1 signals display defects in extraembryonic tissues and germ cell formation. Development 128, 3609–3621.
| PubMed |
van Pelt, A. M. M. , Roepers-Gajadien, H. L. , Gademan, I. S. , Creemers, L. B. , de Rooij, D. G. , and van Dissel-Emiliani, F. M. F. (2002). Establishmnet of cell lines with rat spermatogonial stem cell characteristics. Endocrinology 143, 1845–1850.
| PubMed |
Vecino, P. , Uranga, J. A. , and Arechaga, J. (2001). Suppression of spermatogenesis for cell transplantation in adult mice. Protoplasma 217, 191–198.
| PubMed |
Ventela, S. , Ohta, H. , Parvinen, M. , and Nishimune, Y. (2002). Development of the stages of the cycle in mouse seminiferous epithelium after transplantation of green fluorescent protein-labeled spermatogonial stem cells. Biol. Reprod. 66, 1422–1429.
| PubMed |
Vergouwen, R. P. , Jacobs, S. G. , Huiskamp, R. , Davis, J. A. , and de Rooji, D. G. (1991). Proliferative activity of gonocytes, Sertoli cells and interstitial cells during testicular development in mice. J. Reprod. Fertil. 93, 233–243.
| PubMed |
Vergouwen, R. P. , Hiskamp, R. , Bas, R. J. , Roepers-Gajadien, H. L. , Davis, J. A. , and de Rooji, D. G. (1993). Postnatal development of testicular cell populations in mice. J. Reprod. Fertil. 99, 479–485.
| PubMed |
Wang, X. , Chen, H. , Yin, H. , Kim, S. S. , Tan, S. L. , and Gosden, R. G. (2002). Fertility after intact ovary transplantation. Nature 415, 385.
| Crossref | GoogleScholarGoogle Scholar | PubMed |
Wistuba, J. , Schlatt, S. , Cantauw, C. , von Schonfeldt, V. , Nieschlag, E. , and 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.
| PubMed |
Ying, Y. , Liu, X. M. , Marble, A. , Lawson, K. A. , and Zhao, G. Q. (2000). Requirement of Bmp8b for the generation of primordial germ cells in the mouse. Mol. Endocrinol. 14, 1053–1063.
| PubMed |
Yoshimizu, T. , Obinata, M. , and Matsui, Y. (2001). Stage-specific tissue and cell interactions play key roles in mouse germ cell specification. Development 128, 481–490.
| PubMed |
Zhang, Z. , Renfree, M. B. , and Short, R. V. (2003). Successful intra- and interspecific male germ cell transplantation in the rat. Biol. Reprod. 68, 961–967.
| PubMed |
Zhao, G.-Q. , and Garbers, D. L. (2002). Male germ cell specification and differentiation. Dev. Cell 2, 537–547.
| PubMed |
