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Local signalling environments and human male infertility: what we can learn from mouse models

Published online by Cambridge University Press:  11 May 2010

Roopa L. Nalam
Affiliation:
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA. Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Martin M. Matzuk*
Affiliation:
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA. Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA. Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
*
*Corresponding author: Martin M. Matzuk, Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. E-mail: [email protected]

Abstract

Infertility is one of the most prevalent public health problems facing young adult males in today's society. A clear, treatable cause of infertility cannot be determined in a large number of these patients, and a growing body of evidence suggests that infertility in many of these men may be due to genetic causes. Studies using mouse knockout technology have been integral for examination of normal spermatogenesis and to identify proteins essential for this process, which in turn are candidate genes for human male infertility. Successful spermatogenesis depends on a delicate balance of local signalling factors, and this review focuses on the genes that encode these factors. Normal functioning of all testicular cell types is essential for fertility and might also be crucial to prevent germ cell oncogenesis. Analysis of these signalling processes in spermatogenesis using mouse models has provided investigators with an invaluable tool to effectively translate basic science research to the research of human disease and infertility.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2010

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References

References

1Russell, L.D. and Griswold, M.D. (1993) The Sertoli cell. Cache River Press, ClearwaterGoogle Scholar
2Skinner, M.K. and Griswold, M.D. (2005) Sertoli cell biology. Elsevier Academic Press, AmsterdamGoogle Scholar
3Russell, L.D. (1990) Histological and histopathological evaluation of the testis. Cache River Press, ClearwaterGoogle Scholar
4Matzuk, M.M. and Lamb, D.J. (2008) The biology of infertility: research advances and clinical challenges. Nature Medicine 14, 1197-1213CrossRefGoogle ScholarPubMed
5Yoshida, S., Sukeno, M. and Nabeshima, Y. (2007) A vasculature-associated niche for undifferentiated spermatogonia in the mouse testis. Science 317, 1722-1726CrossRefGoogle ScholarPubMed
6Oatley, J.M. and Brinster, R.L. (2008) Regulation of spermatogonial stem cell self-renewal in mammals. Annual Review of Cell and Developmental Biology 24, 263-286CrossRefGoogle ScholarPubMed
7de Rooij, D.G. (2009) The spermatogonial stem cell niche. Microscopy Research and Technique 72, 580-585CrossRefGoogle ScholarPubMed
8Meng, X. et al. (2000) Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 287, 1489-1493CrossRefGoogle ScholarPubMed
9Yue, F. et al. (2006) Induction of midbrain dopaminergic neurons from primate embryonic stem cells by coculture with sertoli cells. Stem Cells 24, 1695-1706CrossRefGoogle ScholarPubMed
10He, Z. et al. (2007) Gfra1 silencing in mouse spermatogonial stem cells results in their differentiation via the inactivation of RET tyrosine kinase. Biology of Reproduction 77, 723-733CrossRefGoogle ScholarPubMed
11Naughton, C.K. et al. (2006) Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Biology of Reproduction 74, 314-321CrossRefGoogle ScholarPubMed
12Nagano, M. et al. (2003) Maintenance of mouse male germ line stem cells in vitro. Biology of Reproduction 68, 2207-2214CrossRefGoogle ScholarPubMed
13Kubota, H., Avarbock, M.R. and Brinster, R.L. (2004) Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proceedings of the National Academy of Sciences of the United States of America 101, 16489-16494CrossRefGoogle ScholarPubMed
14Kanatsu-Shinohara, M. et al. (2005) Long-term culture of mouse male germline stem cells under serum-or feeder-free conditions. Biology of Reproduction 72, 985-991CrossRefGoogle ScholarPubMed
15Buageaw, A. et al. (2005) GDNF family receptor alpha1 phenotype of spermatogonial stem cells in immature mouse testes. Biology of Reproduction 73, 1011-1016CrossRefGoogle ScholarPubMed
16Ebata, K.T., Zhang, X. and Nagano, M.C. (2005) Expression patterns of cell-surface molecules on male germ line stem cells during postnatal mouse development. Molecular Reproduction and Development 72, 171-181CrossRefGoogle ScholarPubMed
17Jijiwa, M. et al. (2008) GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells. Genes to Cells 13, 365-374CrossRefGoogle ScholarPubMed
18Mauduit, C., Hamamah, S. and Benahmed, M. (1999) Stem cell factor/c-kit system in spermatogenesis. Human Reproduction Update 5, 535-545CrossRefGoogle ScholarPubMed
19Bedell, M.A. and Mahakali Zama, A. (2004) Genetic analysis of Kit ligand functions during mouse spermatogenesis. Journal of Andrology 25, 188-199CrossRefGoogle ScholarPubMed
20Munsie, M. et al. (1997) Expression of stem cell factor in the postnatal rat testis. Molecular Reproduction and Development 47, 19-253.0.CO;2-T>CrossRefGoogle ScholarPubMed
21Yoshinaga, K. et al. (1991) Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function. Development 113, 689-699CrossRefGoogle ScholarPubMed
22Koshimizu, U. et al. (1991) White-spotting mutations affect the regenerative differentiation of testicular germ cells: demonstration by experimental cryptorchidism and its surgical reversal. Biology of Reproduction 45, 642-648CrossRefGoogle ScholarPubMed
23Shinohara, T., Avarbock, M.R. and Brinster, R.L. (1999) beta1- and alpha6-integrin are surface markers on mouse spermatogonial stem cells. Proceedings of the National Academy of Sciences of the United States of America 96, 5504-5509CrossRefGoogle ScholarPubMed
24Prabhu, S.M. et al. (2006) Expression of c-Kit receptor mRNA and protein in the developing, adult and irradiated rodent testis. Reproduction 131, 489-499CrossRefGoogle ScholarPubMed
25Ohta, H. et al. (2000) Regulation of proliferation and differentiation in spermatogonial stem cells: the role of c-kit and its ligand SCF. Development 127, 2125-2131CrossRefGoogle ScholarPubMed
26Ogawa, T. et al. (2000) Transplantation of male germ line stem cells restores fertility in infertile mice. Nature Medicine 6, 29-34CrossRefGoogle ScholarPubMed
27Costoya, J.A. et al. (2004) Essential role of Plzf in maintenance of spermatogonial stem cells. Nature Genetics 36, 653-659CrossRefGoogle ScholarPubMed
28Buaas, F.W. et al. (2004) Plzf is required in adult male germ cells for stem cell self-renewal. Nature Genetics 36, 647-652CrossRefGoogle ScholarPubMed
29Filipponi, D. et al. (2007) Repression of kit expression by Plzf in germ cells. Molecular and Cellular Biology 27, 6770-6781CrossRefGoogle ScholarPubMed
30Ohta, H., Tohda, A. and Nishimune, Y. (2003) Proliferation and differentiation of spermatogonial stem cells in the w/wv mutant mouse testis. Biology of Reproduction 69, 1815-1821CrossRefGoogle ScholarPubMed
31Kubota, H. et al. (2009) Spermatogonial stem cells derived from infertile Wv/Wv mice self-renew in vitro and generate progeny following transplantation. Biology of Reproduction 81, 293-301CrossRefGoogle ScholarPubMed
32Barroca, V. et al. (2009) Mouse differentiating spermatogonia can generate germinal stem cells in vivo. Nature Cell Biology 11, 190-196CrossRefGoogle ScholarPubMed
33Edson, M.A., Nagaraja, A.K. and Matzuk, M.M. (2009) The Mammalian ovary from genesis to revelation. Endocrine Reviews 30, 624-712CrossRefGoogle ScholarPubMed
34Fan, X. et al. (2003) Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retina. Molecular and Cellular Biology 23, 4637-4648CrossRefGoogle ScholarPubMed
35Vernet, N. et al. (2006) Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells. EMBO Journal 25, 5816-5825CrossRefGoogle Scholar
36Niederreither, K. et al. (1999) Embryonic retinoic acid synthesis is essential for early mouse post-implantation development. Nature Genetics 21, 444-448CrossRefGoogle ScholarPubMed
37Bowles, J. et al. (2006) Retinoid signaling determines germ cell fate in mice. Science 312, 596-600CrossRefGoogle ScholarPubMed
38MacLean, G. et al. (2007) Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice. Endocrinology 148, 4560-4567CrossRefGoogle ScholarPubMed
39Ruggiu, M. et al. (1997) The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 389, 73-77CrossRefGoogle ScholarPubMed
40Lin, Y. and Page, D.C. (2005) Dazl deficiency leads to embryonic arrest of germ cell development in XY C57BL/6 mice. Developments in Biologicals 288, 309-316CrossRefGoogle ScholarPubMed
41Anderson, E.L. et al. (2008) Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice. Proceedings of the National Academy of Sciences of the United States of America 105, 14976-14980CrossRefGoogle ScholarPubMed
42Yuan, L. et al. (2000) The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Molecular Cell 5, 73-83CrossRefGoogle ScholarPubMed
43Griswold, M.D. et al. (1989) Function of vitamin A in normal and synchronized seminiferous tubules. Annals of the New York Academy of Sciences 564, 154-172CrossRefGoogle ScholarPubMed
44Bowles, J. et al. (2009) Male-specific expression of Aldh1a1 in mouse and chicken fetal testes: Implications for retinoid balance in gonad development. Developmental Dynamics 238, 2073-2080CrossRefGoogle ScholarPubMed
45Zhou, Q. et al. (2008) Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic cells induced by retinoic acid: an in vivo study in vitamin A-sufficient postnatal murine testes. Biology of Reproduction 79, 35-42CrossRefGoogle Scholar
46Menke, D.B., Koubova, J. and Page, D.C. (2003) Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave. Developments in Biologicals 262, 303-312CrossRefGoogle Scholar
47Seligman, J. and Page, D.C. (1998) The Dazh gene is expressed in male and female embryonic gonads before germ cell sex differentiation. Biochemical and Biophysical Research Communications 245, 878-882CrossRefGoogle ScholarPubMed
48Cooke, H.J. et al. (1996) A murine homologue of the human DAZ gene is autosomal and expressed only in male and female gonads. Human Molecular Genetics 5, 513-516CrossRefGoogle ScholarPubMed
49Lin, Y. et al. (2008) Germ cell-intrinsic and -extrinsic factors govern meiotic initiation in mouse embryos. Science 322, 1685-1687CrossRefGoogle ScholarPubMed
50Reynolds, N. et al. (2007) Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl. RNA 13, 974-981CrossRefGoogle ScholarPubMed
51Kerkhofs, S. et al. (2009) Androgen receptor knockout and knock-in mouse models. Journal of Molecular Endocrinology 42, 11-17CrossRefGoogle ScholarPubMed
52Lyon, M.F. and Hawkes, S.G. (1970) X-linked gene for testicular feminization in the mouse. Nature 227, 1217-1219CrossRefGoogle ScholarPubMed
53He, W.W., Kumar, M.V. and Tindall, D.J. (1991) A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. Nucleic Acids Research 19, 2373-2378CrossRefGoogle ScholarPubMed
54Johnston, H. et al. (2004) Regulation of Sertoli cell number and activity by follicle-stimulating hormone and androgen during postnatal development in the mouse. Endocrinology 145, 318-329CrossRefGoogle ScholarPubMed
55Yeh, S. et al. (2002) Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proceedings of the National Academy of Sciences of the United States of America 99, 13498-13503CrossRefGoogle Scholar
56De Gendt, K. et al. (2004) A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proceedings of the National Academy of Sciences of the United States of America 101, 1327-1332CrossRefGoogle ScholarPubMed
57Chang, C. et al. (2004) Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proceedings of the National Academy of Sciences of the United States of America 101, 6876-6881CrossRefGoogle ScholarPubMed
58Holdcraft, R.W. and Braun, R.E. (2004) Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 131, 459-467CrossRefGoogle ScholarPubMed
59Eacker, S.M. et al. (2007) Transcriptional profiling of androgen receptor (AR) mutants suggests instructive and permissive roles of AR signaling in germ cell development. Molecular Endocrinology 21, 895-907CrossRefGoogle ScholarPubMed
60Denolet, E. et al. (2006) The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice. Molecular Endocrinology 20, 321-334CrossRefGoogle ScholarPubMed
61Wang, R.S. et al. (2006) Androgen receptor in sertoli cell is essential for germ cell nursery and junctional complex formation in mouse testes. Endocrinology 147, 5624-5633CrossRefGoogle ScholarPubMed
62Meng, J. et al. (2005) Androgens regulate the permeability of the blood-testis barrier. Proceedings of the National Academy of Sciences of the United States of America 102, 16696-16700CrossRefGoogle ScholarPubMed
63Lim, P. et al. (2009) Sertoli cell androgen receptor DNA binding domain is essential for the completion of spermatogenesis. Endocrinology 150, 4755-4765CrossRefGoogle ScholarPubMed
64Ferlin, A. et al. (2007) Male infertility: role of genetic background. Reproductive Biomedicine Online 14, 734-745CrossRefGoogle ScholarPubMed
65Krausz, C. and Giachini, C. (2007) Genetic risk factors in male infertility. Archives of Andrology 53, 125-133CrossRefGoogle ScholarPubMed
66Stahl, P.J. et al. (2009) A decade of experience emphasizes that testing for Y microdeletions is essential in American men with azoospermia and severe oligozoospermia. Fertility and Sterility [doi:10.1016/j.fertnstert.2009.09.006]Google ScholarPubMed
67Tung, J.Y. et al. (2006) Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in infertile women and men. Reproductive Biology and Endocrinology 4, 40CrossRefGoogle ScholarPubMed
68Chen, P. et al. (2010) Phenotypic Expression of Partial AZFc Deletions is Independent of the Variations in DAZL and BOULE in a Han Population. Journal of Andrology 31, 163-168CrossRefGoogle Scholar
69Gottlieb, B. et al. (2004) The androgen receptor gene mutations database (ARDB): 2004 update. Human Mutation 23, 527-533CrossRefGoogle ScholarPubMed
70Ferlin, A. et al. (2006) Male infertility and androgen receptor gene mutations: clinical features and identification of seven novel mutations. Clinical Endocrinology 65, 606-610CrossRefGoogle ScholarPubMed
71Yu, Z. et al. (2006) Abnormalities of germ cell maturation and sertoli cell cytoskeleton in androgen receptor 113 CAG knock-in mice reveal toxic effects of the mutant protein. American Journal of Pathology 168, 195-204CrossRefGoogle ScholarPubMed
72Rajender, S., Singh, L. and Thangaraj, K. (2007) Phenotypic heterogeneity of mutations in androgen receptor gene. Asian Journal of Andrology 9, 147-179Google ScholarPubMed
73Looijenga, L.H. (2009) Human testicular (non)seminomatous germ cell tumours: the clinical implications of recent pathobiological insights. Journal of Pathology 218, 146-162CrossRefGoogle ScholarPubMed
74Sonne, S.B. et al. (2008) Testicular dysgenesis syndrome and the origin of carcinoma in situ testis. International Journal of Andrology 31, 275-287CrossRefGoogle ScholarPubMed
75Fisher, J.S. et al. (2003) Human ‘testicular dysgenesis syndrome’: a possible model using in-utero exposure of the rat to dibutyl phthalate. Human Reproduction 18, 1383-1394CrossRefGoogle ScholarPubMed
76Sharpe, R.M. (2006) Pathways of endocrine disruption during male sexual differentiation and masculinization. Best Practice and Research. Clinical Endocrinology and Metabolism 20, 91-110Google Scholar
77Liu, K. et al. (2005) Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Biology of Reproduction 73, 180-192CrossRefGoogle ScholarPubMed
78Swan, S.H. (2008) Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environmental Research 108, 177-184CrossRefGoogle ScholarPubMed
79Heaney, J.D. et al. (2008) Loss of the transmembrane but not the soluble kit ligand isoform increases testicular germ cell tumor susceptibility in mice. Cancer Research 68, 5193-5197CrossRefGoogle Scholar
80Tian, Q. et al. (1999) Activating c-kit gene mutations in human germ cell tumors. American Journal of Pathology 154, 1643-1647CrossRefGoogle ScholarPubMed
81Kemmer, K. et al. (2004) KIT mutations are common in testicular seminomas. American Journal of Pathology 164, 305-313CrossRefGoogle ScholarPubMed
82Looijenga, L.H. et al. (2003) Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors. Cancer Research 63, 7674-7678Google ScholarPubMed
83McIntyre, A. et al. (2005) Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults. Cancer Research 65, 8085-8089CrossRefGoogle ScholarPubMed
84Stoop, H. et al. (2008) Stem cell factor as a novel diagnostic marker for early malignant germ cells. Journal of Pathology 216, 43-54CrossRefGoogle ScholarPubMed
85Blume-Jensen, P. et al. (2000) Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3′-kinase is essential for male fertility. Nature Genetics 24, 157-162CrossRefGoogle ScholarPubMed
86Feng, L.X., Ravindranath, N. and Dym, M. (2000) Stem cell factor/c-kit up-regulates cyclin D3 and promotes cell cycle progression via the phosphoinositide 3-kinase/p70 S6 kinase pathway in spermatogonia. Journal of Biological Chemistry 275, 25572-25576CrossRefGoogle ScholarPubMed
87Jacobsen, R. et al. (2000) Risk of testicular cancer in men with abnormal semen characteristics: cohort study. British Medical Journal 321, 789-792CrossRefGoogle ScholarPubMed
88Peng, X. et al. (2009) The association risk of male subfertility and testicular cancer: a systematic review. PLoS One 4, e5591CrossRefGoogle ScholarPubMed
89Garolla, A. et al. (2005) Molecular analysis of the androgen receptor gene in testicular cancer. Endocrine-Related Cancer 12, 645-655CrossRefGoogle ScholarPubMed
90Nathanson, K.L. et al. (2005) The Y deletion gr/gr and susceptibility to testicular germ cell tumor. American Journal of Human Genetics 77, 1034-1043CrossRefGoogle Scholar
91Grimaldi, P. et al. (2002) Molecular genetics of male infertility: stem cell factor/c-kit system. American Journal of Reproductive Immunology 48, 27-33CrossRefGoogle ScholarPubMed
92Meng, X. et al. (2001) Promotion of seminomatous tumors by targeted overexpression of glial cell line-derived neurotrophic factor in mouse testis. Cancer Research 61, 3267-3271Google ScholarPubMed
93Mai, P.L. et al. (2009) The International Testicular Cancer Linkage Consortium: A clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred. Urologic Oncology [doi:10.1016/j.urolonc.2008.10.004]Google Scholar
94Yu, Z. et al. (2009) Dazl Promotes Germ Cell Differentiation from Embryonic Stem Cells. J Molecular and Cellular Biology 1, 93-103CrossRefGoogle ScholarPubMed
95Kee, K. et al. (2009) Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature 462, 222-225CrossRefGoogle ScholarPubMed
96Tesar, P.J. et al. (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448, 196-199CrossRefGoogle ScholarPubMed
97Rebar, R.W. and DeCherney, A.H. (2004) Assisted reproductive technology in the United States. New England Journal of Medicine 350, 1603-1604CrossRefGoogle ScholarPubMed
98McLachlan, R.I. et al. (1998) Genetic disorders and spermatogenesis. Reproduction Fertility and Development 10, 97-104CrossRefGoogle ScholarPubMed
99Donoso, P., Tournaye, H. and Devroey, P. (2007) Which is the best sperm retrieval technique for non-obstructive azoospermia? A systematic review. Human Reproduction Update 13, 539-549CrossRefGoogle ScholarPubMed
100The Practice Committee of the American Society for Reproductive Medicine (2008) Round spermatid nucleus injection (ROSNI). Fertility and Sterility 90, S199-201CrossRefGoogle Scholar
101Boekelheide, K. and Sigman, M. (2008) Is gene therapy for the treatment of male infertility feasible? Nature Clinical Practice. Urology 5, 590-593CrossRefGoogle ScholarPubMed
102Lamb, D.J. (1999) Debate: is ICSI a genetic time bomb? Yes. Journal of Andrology 20, 23-33CrossRefGoogle ScholarPubMed
103Neri, Q.V., Takeuchi, T. and Palermo, G.D. (2008) An update of assisted reproductive technologies results in the United States. Annals of the New York Academy of Sciences 1127, 41-48CrossRefGoogle ScholarPubMed
104Alukal, J.P. and Lipshultz, L.I. (2008) Safety of assisted reproduction, assessed by risk of abnormalities in children born after use of in vitro fertilization techniques. Nature Clinical Practice Urology 5, 140-150CrossRefGoogle ScholarPubMed
105Alukal, J.P. and Lamb, D.J. (2008) Intracytoplasmic sperm injection (ICSI)–what are the risks? Urologic Clinics of North America 35, 277-288CrossRefGoogle ScholarPubMed
Schultz, N., Hamra, F.K. and Garbers, D.L. (2003) A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proceedings of the National Academy of Sciences of the United States of America 100, 12201-12206CrossRefGoogle ScholarPubMed
Shima, J.E. et al. (2004) The murine testicular transcriptome: characterising gene expression in the testis during the progression of spermatogenesis. Biology of Reproduction 71, 319-330CrossRefGoogle ScholarPubMed
Chalmel, F. et al. (2007) The conserved transcriptome in human and rodent male gametogenesis. Proceedings of the National Academy of Sciences of the United States of America 104, 8346-8351CrossRefGoogle ScholarPubMed
Schultz, N., Hamra, F.K. and Garbers, D.L. (2003) A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proceedings of the National Academy of Sciences of the United States of America 100, 12201-12206CrossRefGoogle ScholarPubMed
Shima, J.E. et al. (2004) The murine testicular transcriptome: characterising gene expression in the testis during the progression of spermatogenesis. Biology of Reproduction 71, 319-330CrossRefGoogle ScholarPubMed
Chalmel, F. et al. (2007) The conserved transcriptome in human and rodent male gametogenesis. Proceedings of the National Academy of Sciences of the United States of America 104, 8346-8351CrossRefGoogle ScholarPubMed