Abstract
Nearly 7% of men suffer from male factor infertility. In one-fourth of infertile males, the etiology remains unexplained. Unlike other multifactorial disorders, gene-gene and gene-environment interactions in the regulation of male fertility have been poorly characterized. A candidate-gene approach that incorporates biological information from model organisms is likely to be critical in deciphering the genetic basis of idiopathic male fertility. Genes that fulfill essential roles in spermatogenesis often have orthologs in several species wherein they serve similar functions. By using a comparative cross-species approach, major susceptibility genes underlying male infertility can be identified in association studies. With a better understanding of the molecular regulation of spermatogenesis, proper diagnosis and treatment of male infertility should be realized in the foreseeable future.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
World Health Organization. Towards more objectivity in diagnosis and management of male infertility. Int J Androl 1987;7:1–53.
Matzuk MM, Lamb DJ. Genetic dissection of mammalian fertility pathways. Nat Med 2002;8:S33–S40.
Special Programme of Research Development and Research Training in Human Reproduction (World Health Organization [WHO]). WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 3rd ed. Published on behalf of the World Health Organization by Cambridge University Press, Cambridge and New York; 1992.
Turek PJ. Practical approaches to the diagnosis and management of male infertility. Nat Clin Pract Urol 2005;2:226–238.
Weber RF, Dohle GR, Romijn JC. Clinical laboratory evaluation of male subfertility. Adv Clin Chem 2005;40:317–364.
Shah K, Sivapalan G, Gibbons N, Tempest H, Griffin DK. The genetic basis of infertility. Reproduction 2003;126:13–25.
Lilford R, Jones AM, Bishop DT, Thornton J, Mueller R. Case-control study of whether subfertility in men is familial. BMJ 1994;309:570–573.
van Golde RJ, van der Avoort IA, Tuerlings JH, et al. Phenotypic characteristics of male subfertility and its familial occurrence. J Androl 2004;25:819–823.
Meschede D, Horst J. The molecular genetics of male infertility. Mol Hum Reprod 1997;3:419–430.
Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 1976;34:119–124.
Huynh T, Mollard R, Trounson A. Selected genetic factors associated with male infertility. Hum Reprod Update 2002;8:183–198.
Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev 2001;22:226–239.
Patrizio P, Leonard DG. Mutations of the cystic fibrosis gene and congenital absence of the vas deferens. Results Probl Cell Differ 2000;28:175–186.
Stuhrmann M, Dork T. CFTR gene mutations and male infertility. Andrologia 2000;32:71–83.
Cooke HJ, Saunders PT. Mouse models of male infertility. Nat Rev Genet 2002;3:790–801.
Hirschhorn JN, Daly MJ. Genome-wide association studies for common diseases and complex traits. Nat Rev Genet 2005;6:95–108.
Gianotten J, Lombardi MP, Zwinderman AH, Lilford RJ, van der Veen F. Idiopathic impaired spermatogenesis: genetic epidemiology is unlikely to provide a short-cut to better understanding. Hum Reprod Update 2004;10:533–539.
Altshuler D, Brooks LD, Chakravarti A, Collins FS, Daly MJ, Donnelly P. A haplotype map of the human genome. Nature 2005;437:1299–1320.
Cardon LR, Bell JI. Association study designs for complex diseases. Nat Rev Genet 2001;2:91–99.
Yuan L, Liu JG, Zhao J, Brundell E, Daneholt B, Hoog C. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 2000;5:73–83.
Miyamoto T, Hasuike S, Yogev L, et al. Azoospermia in patients heterozygous for a mutation in SYCP3. Lancet 2003;362:1714–1719.
Ruggiu M, Speed R, Taggart M, et al. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 1997;389:73–77.
Tung JY, Rosen MP, Nelson LM, et al. Variants in deleted in AZoospermia-like (DAZL) are correlated with reproductive parameters in men and women. Hum Genet 2006;118:730–740.
Cho C, Willis WD, Goulding EH, et al. Haploinsufficiency of protamine-1 or-2 causes infertility in mice. Nat Genet 2001;28:82–86.
de Yebra L, Ballesca JL, Vanrell JA, Bassas L, Oliva R. Complete selective absence of protamine P2 in humans. J Biol Chem 1993;268:10,553–10,557.
Tanaka H, Miyagawa Y, Tsujimura A, Matsumiya K, Okuyama A, Nishimune Y. Single nucleotide polymorphisms in the protamine-1 and-2 genes of fertile and infertile human male populations. Mol Hum Reprod 2003;9:69–73.
Iguchi N, Yang S, Lamb DJ, Hecht NB. A protamine SNP: one genetic cause of male infertility. J Med Genet 2006;43:382–384.
Yu YE, Zhang Y, Unni E, et al. Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice. Proc Natl Acad Sci USA 2000;97:4683–4688.
Zhao M, Shirley CR, Hayashi S, et al. Transition nuclear proteins are required for normal chromatin condensation and functional sperm development. Genesis 2004;38:200–213.
Miyagawa Y, Nishimura H, Tsujimura A, et al. Single-nucleotide polymorphisms and mutation analyses of the TNP1 and TNP2 genes of fertile and infertile human male populations. J Androl 2005;26:779–786.
Galan JJ, Buch B, Cruz N, et al. Multilocus analyses of estrogen-related genes reveal involvement of the ESR1 gene in male infertility and the polygenic nature of the pathology. Fertil Steril 2005;84:910–918.
Eddy EM, O’Brien DA. Gene expression during mammalian meiosis. Curr Top Dev Biol 1998;37:141–200.
Kleene KC. Sexual selection, genetic conflict, selfish genes, and the atypical patterns of gene expression in spermatogenic cells. Dev Biol 2005;277:16–26.
Adams MD, Kelley JM, Gocayne JD, et al. Complementary DNA sequencing: expressed sequence tags and human genome project. Science 1991;252:1651–1656.
Okubo K, Hori N, Matoba R, et al. Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression. Nat Genet 1992;2:173–179.
Wilcox AS, Khan AS, Hopkins JA, Sikela JM. Use of 3′ untranslated sequences of human cDNAs for rapid chromosome assignment and conversion to STSs: implications for an expression map of the genome. Nucleic Acids Res 1991;19:1837–1843.
Boguski MS, Schuler GD. ESTablishing a human transcript map. Nat Genet 1995;10:369–371.
Strausberg RL, Dahl CA, Klausner RD. New opportunities for uncovering the molecular basis of cancer. Nat Genet 1997;15:415–416.
Huminiecki L, Bicknell R. In silico cloning of novel endothelial-specific genes. Genome Res 2000;10:1796–1806.
Rajkovic A, Yan MSC, Klysik M, Matzuk M. Discovery of germ cell-specific transcripts by expressed sequence tag database analysis. Fertil Steril 2001;76:550–554.
Hedges SB. The origin and evolution of model organisms. Nat Rev Genet 2002;3:838–849.
Lin YN, Matzuk MM. High-throughput discovery of germ-cell-specific genes. Semin Reprod Med 2005;23:201–212.
Yan W, Ma L, Burns KH, Matzuk MM. Haploinsufficiency of kelch-like protein homolog 10 causes infertility in male mice. Proc Natl Acad Sci USA 2004;101:7793–7798.
Hinrichs AS, Karolchik D, Baertsch R, et al. The UCSC Genome Browser Database: update 2006. Nucleic Acids Res 2006;34:D590–D598.
Finn RD, Mistry J, Schuster-Bockler B, et al. Pfam: clans, web tools and services. Nucleic Acids Res 2006;34:D247–D251.
Letunic I, Copley RR, Schmidt S, et al. SMART 4.0: towards genomic data integration. Nucleic Acids Res 2004;32:D142–D144.
Devroey P, Van Steirteghem A. A review of ten years experience of ICSI. Hum Reprod Update 2004;10:19–28.
Savolainen P, Fitzsimmons C, Arvestad L, Andersson L, Lundeberg J. ESTs from brain and testis of White Leghorn and red junglefowl: annotation, bioinformatic classification of unknown transcripts and analysis of expression levels. Cytogenet Genome Res 2005;111:79–87.
Shin JH, Kim H, Song KD, et al. A set of testis-specific novel genes collected from a collection of Korean Native Chicken ESTs. Anim Genet 2005;36:346–348.
Zeng S, Gong Z. Expressed sequence tag analysis of expression profiles of zebrafish testis and ovary. Gene 2002;294:45–53.
Inaba K, Padma P, Satouh Y, et al. EST analysis of gene expression in testis of the ascidian Ciona intestinalis. Mol Reprod Dev 2002;62:431–445.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this chapter
Cite this chapter
Roy, A., Lin, YN., Matzuk, M.M. (2007). Genetics of Idiopathic Male Infertility. In: Carrell, D.T. (eds) The Genetics of Male Infertility. Humana Press. https://doi.org/10.1007/978-1-59745-176-5_6
Download citation
DOI: https://doi.org/10.1007/978-1-59745-176-5_6
Publisher Name: Humana Press
Print ISBN: 978-1-58829-863-8
Online ISBN: 978-1-59745-176-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)