Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-v5vhk Total loading time: 0 Render date: 2024-07-05T22:07:41.116Z Has data issue: false hasContentIssue false

14 - The Genetic Basis of Male Infertility

Published online by Cambridge University Press:  25 May 2017

By
Amin S. Herati ,
Peter R. Butler  and
Dolores J. Lamb
Edited by
Christopher J. De Jonge  and
Christopher L. R. Barratt
Foreword by
Ryuzo Yanagimachi
Christopher J. De Jonge
Affiliation:
University of Minnesota
Christopher L. R. Barratt
Affiliation:
University of Dundee
Ryuzo Yanagimachi
Affiliation:
University of Hawaii, Manoa
Get access

Summary

A summary is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Image of the first page of this content. For PDF version, please use the ‘Save PDF’ preceeding this image.'
Type
Chapter
Information
The Sperm Cell
Production, Maturation, Fertilization, Regeneration
 , pp. 208 - 229
Publisher: Cambridge University Press
Print publication year: 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

de Kretser, DM. Male infertility. Lancet 1997; 349: 787–90.CrossRefGoogle ScholarPubMed
Guzick, DS, Overstreet, JW, Factor-Litvak, P, Brazil, CK, Nakajima, ST, Coutifaris, C, et al. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 2001; 345: 1,388–93.CrossRefGoogle ScholarPubMed
Dohle, GR, Colpi, GM, Hargreave, TB, Papp, GK, Jungwirth, A, Weidner, W, et al. EAU guidelines on male infertility. Eur Urol 2005; 48: 703–11.CrossRefGoogle ScholarPubMed
Hwang, K, Yatsenko, AN, Jorgez, CJ, Mukherjee, S, Nalam, RL, Matzuk, MM, et al. Mendelian genetics of male infertility. Ann NY Acad Sci 2010; 1,214: E1–E17.Google Scholar
Tjio, JH, Levan, A. The chromosome number of man. Hereditas 1956; 42: 1–6.CrossRefGoogle Scholar
Yatsenko, AN, Yatsenko, SA, Weedin, JW, Lawrence, AE, Patel, A, Peacock, S, et al. Comprehensive 5-year study of cytogenetic aberrations in 668 infertile men. J Urol 2010; 183: 1,636–42.CrossRefGoogle ScholarPubMed
Elghezal, H, Hidar, S, Braham, R, Denguezli, W, Ajina, M, Saad, A. Chromosome abnormalities in one thousand infertile males with nonobstructive sperm disorders. Fertil Steril 2006; 86: 1,792–5.CrossRefGoogle ScholarPubMed
Ceylan, GG, Ceylan, C, Elyas, H. Genetic anomalies in patients with severe oligozoospermia and azoospermia in eastern Turkey: A prospective study. Genet Mol Res 2009; 8: 915–22.CrossRefGoogle ScholarPubMed
Berger, R. [The incidence of constitutional chromosome aberrations]. J Genet Hum 1975; 23 Suppl: 42–9.Google ScholarPubMed
Baer, RJ, Flessel, MC, Jelliffe-Pawlowski, LL, Goldman, S, Hudgins, L, Hull, AD, et al. Detection rates for aneuploidy by first-trimester and sequential screening. Obstet Gynecol 2015; 126: 753–9.CrossRefGoogle ScholarPubMed
Retief, AE, Van Zyl, JA, Menkveld, R, Fox, MF, Kotze, GM, Brusnicky, J. Chromosome studies in 496 infertile males with a sperm count below 10 million/ml. Hum Genet 1984; 66: 162–4.CrossRefGoogle ScholarPubMed
Bourrouillou, G, Dastugue, N, Colombies, P. Chromosome studies in 952 infertile males with a sperm count below 10 million/ml. Hum Genet 1985; 71: 366–7.CrossRefGoogle ScholarPubMed
Chandley, AC. The chromosomal basis of human infertility. Br Med Bull 1979; 35: 181–6.CrossRefGoogle ScholarPubMed
Kosar, PA, Ozcelik, N, Kosar, A. Cytogenetic abnormalities detected in patients with non-obstructive azoospermia and severe oligozoospermia. J Assist Reprod Genet 2010; 27: 17–21.CrossRefGoogle ScholarPubMed
Abramsson, L, Beckman, G, Duchek, M, Nordenson, I. Chromosomal aberrations and male infertility. J Urol 1982; 128: 52–3.CrossRefGoogle ScholarPubMed
Van Assche, E, Bonduelle, M, Tournaye, H, Joris, H, Verheyen, G, Devroey, P, et al. Cytogenetics of infertile men. Hum Reprod 1996; 11 Suppl 4: 1–24; discussion 5–6.CrossRefGoogle ScholarPubMed
Tempest, HG. Meiotic recombination errors, the origin of sperm aneuploidy and clinical recommendations. Syst Biol Reprod Med 2011; 57: 93–101.CrossRefGoogle ScholarPubMed
Hassold, T, Hunt, PA, Sherman, S. Trisomy in humans: Incidence, origin and etiology. Curr Opin Genet Dev 1993; 3: 398–403.CrossRefGoogle ScholarPubMed
Jedraszak, G, Copin, H, Demailly, M, Quibel, C, Leclerc, T, Gallet, M, et al. Azoospermia and trisomy 18p syndrome: A fortuitous association? A patient report and a review of the literature. Mol Cytogenet 2015; 8: 34.CrossRefGoogle Scholar
Bobrow, M, Barby, T, Hajianpour, A, Maxwell, D, Yau, SC. Fertility in a male with trisomy 21. J Med Genet 1992; 29: 141.CrossRefGoogle Scholar
Sheridan, R, Llerena, J Jr., Matkins, S, Debenham, P, Cawood, A, Bobrow, M. Fertility in a male with trisomy 21. J Med Genet 1989; 26: 294–8.CrossRefGoogle Scholar
Pradhan, M, Dalal, A, Khan, F, Agrawal, S. Fertility in men with Down syndrome: A case report. Fertil Steril 2006; 86: 1,765 e1–3.CrossRefGoogle ScholarPubMed
Johannisson, R, Gropp, A, Winking, H, Coerdt, W, Rehder, H, Schwinger, E. Down's syndrome in the male. Reproductive pathology and meiotic studies. Hum Genet 1983; 63: 132–8.CrossRefGoogle ScholarPubMed
Shah, K, Sivapalan, G, Gibbons, N, Tempest, H, Griffin, DK. The genetic basis of infertility. Reproduction 2003; 126: 13–25.CrossRefGoogle ScholarPubMed
Groth, KA, Skakkebaek, A, Host, C, Gravholt, CH, Bojesen, A. Clinical review: Klinefelter syndrome – A clinical update. J Clin Endocrinol Metab 2013; 98: 20–30.CrossRefGoogle ScholarPubMed
Nielsen, J, Wohlert, M. Chromosome abnormalities found among 34,910 newborn children: Results from a 13-year incidence study in Arhus, Denmark. Hum Genet 1991; 87: 81–3.CrossRefGoogle ScholarPubMed
Gekas, J, Thepot, F, Turleau, C, Siffroi, JP, Dadoune, JP, Briault, S, et al. Chromosomal factors of infertility in candidate couples for ICSI: An equal risk of constitutional aberrations in women and men. Hum Reprod 2001; 16: 82–90.CrossRefGoogle ScholarPubMed
Ferlin, A, Arredi, B, Foresta, C. Genetic causes of male infertility. Reprod Toxicol 2006; 22: 133–41.CrossRefGoogle ScholarPubMed
Lanfranco, F, Kamischke, A, Zitzmann, M, Nieschlag, E. Klinefelter's syndrome. Lancet 2004; 364: 273–83.CrossRefGoogle ScholarPubMed
Hassold, TJ, Sherman, SL, Pettay, D, Page, DC, Jacobs, PA. XY chromosome nondisjunction in man is associated with diminished recombination in the pseudoautosomal region. Am J Hum Genet 1991; 49: 253–60.Google Scholar
Thomas, NS, Hassold, TJ. Aberrant recombination and the origin of Klinefelter syndrome. Hum Reprod Update 2003; 9: 309–17.CrossRefGoogle ScholarPubMed
Vallabhajosyula, R, Rajangam, S, Lalitha, C. Association of parental origin with clinical profile in Klinefelter syndrome. J Clin Diagn Res 2015; 9: GC01–3.Google ScholarPubMed
Ottesen, AM, Aksglaede, L, Garn, I, Tartaglia, N, Tassone, F, Gravholt, CH et al. Increased number of sex chromosomes affects height in a nonlinear fashion: A study of 305 patients with sex chromosome aneuploidy. Am J Med Genet A 2010; 152A: 1,206–12.CrossRefGoogle Scholar
Rocca, MS, Pecile, V, Cleva, L, Speltra, E, Selice, R, Di Mambro, A et al. The Klinefelter syndrome is associated with high recurrence of copy number variations on the X chromosome with a potential role in the clinical phenotype. Andrology 2016; 4: 328–34.CrossRefGoogle ScholarPubMed
Simanainen, U, Brogley, M, Gao, YR, Jimenez, M, Harwood, DT, Handelsman, DJ, et al. Length of the human androgen receptor glutamine tract determines androgen sensitivity in vivo. Mol Cell Endocrinol 2011; 342: 81–6.CrossRefGoogle ScholarPubMed
Zitzmann, M, Depenbusch, M, Gromoll, J, Nieschlag, E. X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J Clin Endocrinol Metab 2004; 89: 6,208–17.CrossRefGoogle ScholarPubMed
Davis-Dao, CA, Tuazon, ED, Sokol, RZ, Cortessis, VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: A meta-analysis. J Clin Endocrinol Metab 2007; 92: 4,319–26.CrossRefGoogle ScholarPubMed
Mifsud, A, Sim, CK, Boettger-Tong, H, Moreira, S, Lamb, DJ, Lipshultz, LI, et al. Trinucleotide (CAG) repeat polymorphisms in the androgen receptor gene: Molecular markers of risk for male infertility. Fertil Steril 2001; 75: 275–81.CrossRefGoogle ScholarPubMed
Aksglaede, L, Wikstrom, 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.CrossRefGoogle ScholarPubMed
Mau-Holzmann, UA. Somatic chromosomal abnormalities in infertile men and women. Cytogenet Genome Res 2005; 111: 317–36.CrossRefGoogle ScholarPubMed
Rives, N, Milazzo, JP, Perdrix, A, Castanet, M, Joly-Helas, G, Sibert, L et al. The feasibility of fertility preservation in adolescents with Klinefelter syndrome. Hum Reprod 2013; 28: 1,468–79.CrossRefGoogle ScholarPubMed
Ramasamy, R, Ricci, JA, Palermo, GD, Gosden, LV, Rosenwaks, Z, Schlegel, PN. Successful fertility treatment for Klinefelter's syndrome. J Urol 2009; 182: 1,108–13.CrossRefGoogle ScholarPubMed
Liehr, T, Weise, A. Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med 2007; 19: 719–31.Google ScholarPubMed
Armanet, N, Tosca, L, Brisset, S, Liehr, T, Tachdjian, G. Small supernumerary marker chromosomes in human infertility. Cytogenet Genome Res 2015; 146: 100–8.CrossRefGoogle ScholarPubMed
Sarrate, Z, Blanco, J, Anton, E, Egozcue, S, Egozcue, J, Vidal, F. FISH studies of chromosome abnormalities in germ cells and its relevance in reproductive counseling. Asian J Androl 2005; 7: 227–36.CrossRefGoogle ScholarPubMed
Douet-Guilbert, N, Bris, MJ, Amice, V, Marchetti, C, Delobel, B, Amice, J et al. Interchromosomal effect in sperm of males with translocations: Report of 6 cases and review of the literature. Int J Androl 2005; 28: 372–9.CrossRefGoogle ScholarPubMed
Tempest, HG, Cheng, SY, Gillott, DJ, Handyside, AH, Thornhill, AR, Griffin, DK. Scoring of sperm chromosomal abnormalities by manual and automated approaches: Qualitative and quantitative comparisons. Asian J Androl 2010; 12: 257–62.CrossRefGoogle ScholarPubMed
Madan, K. Balanced structural changes involving the human X: Effect on sexual phenotype. Hum Genet 1983; 63: 216–21.CrossRefGoogle ScholarPubMed
Mohandas, TK, Speed, RM, Passage, MB, Yen, PH, Chandley, AC, Shapiro, LJ. Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: Meiotic studies in a man with a deletion of distal Xp. Am J Hum Genet 1992; 51: 526–33.Google Scholar
Oliver-Bonet, M, Benet, J, Sun, F, Navarro, J, Abad, C, Liehr, T et al. Meiotic studies in two human reciprocal translocations and their association with spermatogenic failure. Hum Reprod 2005; 20: 683–8.CrossRefGoogle ScholarPubMed
Rosenmann, A, Wahrman, J, Richler, C, Voss, R, Persitz, A, Goldman, B. Meiotic association between the XY chromosomes and unpaired autosomal elements as a cause of human male sterility. Cytogenet Cell Genet 1985; 39: 19–29.CrossRefGoogle ScholarPubMed
Gabriel-Robez, O, Ratomponirina, C, Dutrillaux, B, Carre-Pigeon, F, Rumpler, Y. Meiotic association between the XY chromosomes and the autosomal quadrivalent of a reciprocal translocation in two infertile men, 46,XY,t(19;22) and 46,XY,t(17;21). Cytogenet Cell Genet 1986; 43: 154–60.CrossRefGoogle Scholar
Chandley, AC, McBeath, S, Speed, RM, Yorston, L, Hargreave, TB. Pericentric inversion in human chromosome 1 and the risk for male sterility. J Med Genet 1987; 24: 325–34.CrossRefGoogle ScholarPubMed
Rives, N. Y chromosome microdeletions and alterations of spermatogenesis, patient approach and genetic counseling. Ann Endocrinol (Paris) 2014; 75: 112–4.CrossRefGoogle ScholarPubMed
Vogt, PH. Azoospermia factor (AZF) in Yq11: Towards a molecular understanding of its function for human male fertility and spermatogenesis. Reprod Biomed Online 2005; 10: 81–93.CrossRefGoogle ScholarPubMed
Lange, J, Skaletsky, H, van Daalen, SK, Embry, SL, Korver, CM, Brown, LG et al. Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes. Cell 2009; 138: 855–69.CrossRefGoogle ScholarPubMed
Navarro-Costa, P, Plancha, CE, Goncalves, J. Genetic dissection of the AZF regions of the human Y chromosome: Thriller or filler for male (in)fertility? J Biomed Biotechnol 2010; 2010: 936569.CrossRefGoogle ScholarPubMed
Jorgez, CJ, Weedin, JW, Sahin, A, Tannour-Louet, M, Han, S, Bournat, JC et al. Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome microdeletions. J Clin Endocrinol Metab 2011; 96: E674–9.CrossRefGoogle ScholarPubMed
Tiepolo, L, Zuffardi, O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 1976; 34: 119–24.CrossRefGoogle ScholarPubMed
Vogt, PH, Edelmann, A, Kirsch, S, Henegariu, O, Hirschmann, P, Kiesewetter, F et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet 1996; 5: 933–43.CrossRefGoogle ScholarPubMed
Repping, S, Skaletsky, H, Lange, J, Silber, S, Van Der Veen, F, Oates, RD et al. Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure. Am J Hum Genet 2002; 71: 906–22.CrossRefGoogle ScholarPubMed
Massart, A, Lissens, W, Tournaye, H, Stouffs, K. Genetic causes of spermatogenic failure. Asian J Androl 2012; 14: 40–8.CrossRefGoogle ScholarPubMed
Foresta, C, Moro, E, Ferlin, A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev 2001; 22: 226–39.Google ScholarPubMed
Krausz, C, Hoefsloot, L, Simoni, M, Tuttelmann, F, European Academy of Andrology, European Molecular Genetics Quality Network. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: State-of-the-art 2013. Andrology 2014; 2: 5–19.CrossRefGoogle ScholarPubMed
Foresta, C, Moro, E, Ferlin, A. Prognostic value of Y deletion analysis. The role of current methods. Hum Reprod 2001; 16: 1,543–7.CrossRefGoogle ScholarPubMed
Yu, XW, Wei, ZT, Jiang, YT, Zhang, SL. Y chromosome azoospermia factor region microdeletions and transmission characteristics in azoospermic and severe oligozoospermic patients. Int J Clin Exp Med 2015; 8: 14,634–46.Google ScholarPubMed
Luddi, A, Margollicci, M, Gambera, L, Serafini, F, Cioni, M, De Leo, V et al. Spermatogenesis in a man with complete deletion of USP9Y. N Engl J Med 2009; 360: 881–5.CrossRefGoogle Scholar
Akimoto, C, Kitagawa, H, Matsumoto, T, Kato, S. Spermatogenesis-specific association of SMCY and MSH5. Genes Cells 2008; 13: 623–33.CrossRefGoogle ScholarPubMed
Shinka, T, Sato, Y, Chen, G, Naroda, T, Kinoshita, K, Unemi, Y et al. Molecular characterization of heat shock-like factor encoded on the human Y chromosome, and implications for male infertility. Biol Reprod 2004; 71: 297–306.CrossRefGoogle ScholarPubMed
Kichine, E, Roze, V, Di Cristofaro, J, Taulier, D, Navarro, A, Streichemberger, E et al. HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome are not required for spermatocyte maturation. Hum Reprod 2012; 27: 615–24.CrossRefGoogle Scholar
Soares, AR, Costa, P, Silva, J, Sousa, M, Barros, A, Fernandes, S. AZFb microdeletions and oligozoospermia – Which mechanisms? Fertil Steril 2012; 97: 858–63.CrossRefGoogle ScholarPubMed
Fu, XF, Cheng, SF, Wang, LQ, Yin, S, De Felici, M, Shen, W. DAZ Family proteins, key players for germ cell development. Int J Biol Sci 2015; 11: 1,226–35.CrossRefGoogle ScholarPubMed
Fernandes, AT, Fernandes, S, Goncalves, R, Sa, R, Costa, P, Rosa, A et al. DAZ gene copies: Evidence of Y chromosome evolution. Mol Hum Reprod 2006; 12: 519–23.CrossRefGoogle ScholarPubMed
Kleiman, SE, Yogev, L, Hauser, R, Botchan, A, Bar-Shira Maymon, B, Schreiber, L et al. Members of the CDY family have different expression patterns: CDY1 transcripts have the best correlation with complete spermatogenesis. Hum Genet 2003; 113: 486–92.CrossRefGoogle ScholarPubMed
Tuttelmann, F, Rajpert-De Meyts, E, Nieschlag, E, Simoni, M. Gene polymorphisms and male infertility – A meta-analysis and literature review. Reprod Biomed Online 2007; 15: 643–58.CrossRefGoogle ScholarPubMed
Zhu, Z, Li, C, Yang, S, Tian, R, Wang, J, Yuan, Q et al. Dynamics of the transcriptome during human spermatogenesis: Predicting the potential key genes regulating male gametes generation. Sci Rep 2016; 6: 19,069.CrossRefGoogle ScholarPubMed
Kaplan, E, Shwachman, H, Perlmutter, AD, Rule, A, Khaw, KT, Holsclaw, DS. Reproductive failure in males with cystic fibrosis. N Engl J Med 1968; 279: 65–9.CrossRefGoogle ScholarPubMed
Tizzano, EF, Chitayat, D, Buchwald, M. Cell-specific localization of CFTR mRNA shows developmentally regulated expression in human fetal tissues. Hum Mol Genet 1993; 2: 219–24.CrossRefGoogle ScholarPubMed
Chillon, M, Casals, T, Mercier, B, Bassas, L, Lissens, W, Silber, S et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995; 332: 1,475–80.CrossRefGoogle ScholarPubMed
Franco, B, Guioli, S, Pragliola, A, Incerti, B, Bardoni, B, Tonlorenzi, R et al. A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. Nature 1991; 353: 529–36.CrossRefGoogle ScholarPubMed
Young, J, Metay, C, Bouligand, J, Tou, B, Francou, B, Maione, L et al. SEMA3A deletion in a family with Kallmann syndrome validates the role of semaphorin 3A in human puberty and olfactory system development. Hum Reprod 2012; 27: 1,460–5.CrossRefGoogle Scholar
Dode, C, Levilliers, J, Dupont, JM, De Paepe, A, Le Du, N, Soussi-Yanicostas, N et al. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet 2003; 33: 463–5.CrossRefGoogle ScholarPubMed
Seminara, SB, Messager, S, Chatzidaki, EE, Thresher, RR, Acierno, JS Jr, Shagoury, JK et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003; 349: 1,614–27.CrossRefGoogle ScholarPubMed
Hildebrand, MS, Avenarius, MR, Fellous, M, Zhang, Y, Meyer, NC, Auer, J et al. Genetic male infertility and mutation of CATSPER ion channels. Eur J Hum Genet 2010; 18: 1,178–84.CrossRefGoogle ScholarPubMed
Satokata, I, Benson, G, Maas, R. Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice. Nature 1995; 374: 460–3.CrossRefGoogle ScholarPubMed
Afzelius, BA, Eliasson, R, Johnsen, O, Lindholmer, C. Lack of dynein arms in immotile human spermatozoa. J Cell Biol 1975; 66: 225–32.CrossRefGoogle ScholarPubMed
Sha, YW, Ding, L, Li, P. Management of primary ciliary dyskinesia/Kartagener's syndrome in infertile male patients and current progress in defining the underlying genetic mechanism. Asian J Androl 2014; 16: 101–6.Google ScholarPubMed
Moore, DJ, Onoufriadis, A, Shoemark, A, Simpson, MA, zur Lage, PI, de Castro, SC et al. Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia. Am J Hum Genet 2013; 93: 346–56.CrossRefGoogle ScholarPubMed
Olbrich, H, Schmidts, M, Werner, C, Onoufriadis, A, Loges, NT, Raidt, J et al. Recessive HYDIN mutations cause primary ciliary dyskinesia without randomization of left-right body asymmetry. Am J Hum Genet 2012; 91: 672–84.CrossRefGoogle ScholarPubMed
Fliegauf, M, Benzing, T, Omran, H. When cilia go bad: Cilia defects and ciliopathies. Nat Rev Mol Cell Biol 2007; 8: 880–93.CrossRefGoogle ScholarPubMed
Linck, RW, Chemes, H, Albertini, DF. The axoneme: The propulsive engine of spermatozoa and cilia and associated ciliopathies leading to infertility. J Assist Reprod Genet 2016; 33: 141–56.CrossRefGoogle ScholarPubMed
Marshall, CR, Scherer, SW, Zariwala, MA, Lau, L, Paton, TA, Stockley, T et al. Whole-exome sequencing and targeted copy number analysis in primary ciliary dyskinesia. G3 (Bethesda) 2015; 5: 1,775–81.CrossRefGoogle ScholarPubMed
Koscinski, I, Elinati, E, Fossard, C, Redin, C, Muller, J, Velez de la Calle, J et al. DPY19L2 deletion as a major cause of globozoospermia. Am J Hum Genet 2011; 88: 344–50.CrossRefGoogle Scholar
Kuentz, P, Vanden Meerschaut, F, Elinati, E, Nasr-Esfahani, MH, Gurgan, T, Iqbal, N et al. Assisted oocyte activation overcomes fertilization failure in globozoospermic patients regardless of the DPY19L2 status. Hum Reprod 2013; 28: 1,054–61.CrossRefGoogle ScholarPubMed
Erzurumluoglu, AM, Shihab, HA, Rodriguez, S, Gaunt, TR, Day, IN. Importance of genetic studies in consanguineous populations for the characterization of novel human gene functions. Ann Hum Genet 2016; 80: 187–96.CrossRefGoogle ScholarPubMed
Choi, Y, Jeon, S, Choi, M, Lee, MH, Park, M, Lee, DR et al. Mutations in SOHLH1 gene associate with nonobstructive azoospermia. Hum Mutat 2010; 31: 788–93.CrossRefGoogle ScholarPubMed
Miyamoto, T, Hasuike, S, Yogev, L, Maduro, MR, Ishikawa, M, Westphal, H et al. Azoospermia in patients heterozygous for a mutation in SYCP3. Lancet 2003; 362: 1,714–9.CrossRefGoogle ScholarPubMed
Ropke, A, Tewes, AC, Gromoll, J, Kliesch, S, Wieacker, P, Tuttelmann, F. Comprehensive sequence analysis of the NR5A1 gene encoding steroidogenic factor 1 in a large group of infertile males. Eur J Hum Genet 2013; 21: 1,012–5.CrossRefGoogle Scholar
Mou, L, Wang, Y, Li, H, Huang, Y, Jiang, T, Huang, W et al. A dominant-negative mutation of HSF2 associated with idiopathic azoospermia. Hum Genet 2013; 132: 159–65.CrossRefGoogle ScholarPubMed
Imken, L, Rouba, H, El Houate, B, Louanjli, N, Barakat, A, Chafik, A et al. Mutations in the protamine locus: association with spermatogenic failure? Mol Hum Reprod 2009; 15: 733–8.CrossRefGoogle ScholarPubMed
Yatsenko, AN, Georgiadis, AP, Ropke, A, Berman, AJ, Jaffe, T, Olszewska, M et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med 2015; 372: 2,097–107.CrossRefGoogle ScholarPubMed
Jorgez, CJ, Wilken, N, Addai, JB, Newberg, J, Vangapandu, HV, Pastuszak, AW et al. Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia. Fertil Steril 2015; 103: 44–52 e1.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Derrien, T, Johnson, R, Bussotti, G, Tanzer, A, Djebali, S, Tilgner, H et al. The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res 2012; 22: 1,775–89.CrossRefGoogle ScholarPubMed
HSPA2.Available at http://www.genecards.org/cgi-bin/carddisp.pl?gene=HSPA2&keywords=HSPA2. Accessed April 5, 2016.Google Scholar
Wang, G, Ying, Z, Jin, X, Tu, N, Zhang, Y, Phillips, M et al. Essential requirement for both hsf1 and hsf2 transcriptional activity in spermatogenesis and male fertility. Genesis 2004; 38: 66–80.CrossRefGoogle ScholarPubMed
Aoki, VW, Liu, L, Carrell, DT. Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Hum Reprod 2005; 20: 1,298–830.CrossRefGoogle Scholar
Braun, RE. Packaging paternal chromosomes with protamine. Nat Genet 2001; 28: 10–2.CrossRefGoogle ScholarPubMed
Jiang, W, Sun, H, Zhang, J, Zhou, Q, Wu, Q, Li, T et al. Polymorphisms in Protamine 1 and Protamine 2 predict the risk of male infertility: A meta-analysis. Sci Rep 2015; 5: 15,300.CrossRefGoogle ScholarPubMed
Jenkins, TG, Carrell, DT. The sperm epigenome and potential implications for the developing embryo. Reproduction 2012; 143: 727–34.CrossRefGoogle ScholarPubMed
Laiho, A, Kotaja, N, Gyenesei, A, Sironen, A. Transcriptome profiling of the murine testis during the first wave of spermatogenesis. PloS One 2013; 8: e61558.CrossRefGoogle ScholarPubMed
Chalmel, F, Rolland, AD, Niederhauser-Wiederkehr, C, Chung, SS, Demougin, P, Gattiker, A et al. The conserved transcriptome in human and rodent male gametogenesis. Proc Natl Acad Sci USA 2007; 104: 8,346–51.CrossRefGoogle ScholarPubMed
Pessot, CA, Brito, M, Figueroa, J, Concha, II, Yanez, A, Burzio, LO. Presence of RNA in the sperm nucleus. Biochem Biophys Res Commun 1989; 158: 272–8.CrossRefGoogle ScholarPubMed
Modi, D, Shah, C, Sachdeva, G, Gadkar, S, Bhartiya, D, Puri, C. Ontogeny and cellular localization of SRY transcripts in the human testes and its detection in spermatozoa. Reproduction 2005; 130: 603–13.CrossRefGoogle ScholarPubMed
Kumar, G, Patel, D, Naz, RK. c-MYC mRNA is present in human sperm cells. Cell Mol Biol Res 1993; 39: 111–7.Google ScholarPubMed
Dadoune, JP, Siffroi, JP, Alfonsi, MF. Transcription in haploid male germ cells. Int Rev Cytol 2004; 237: 1–56.CrossRefGoogle ScholarPubMed
Soumillon, M, Necsulea, A, Weier, M, Brawand, D, Zhang, X, Gu, H et al. Cellular source and mechanisms of high transcriptome complexity in the mammalian testis. Cell Rep 2013; 3: 2,179–90.CrossRefGoogle ScholarPubMed
Lian, J, Zhang, X, Tian, H, Liang, N, Wang, Y, Liang, C et al. Altered microRNA expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol 2009; 7: 13.CrossRefGoogle ScholarPubMed
Abu-Halima, M, Backes, C, Leidinger, P, Keller, A, Lubbad, AM, Hammadeh, M et al. MicroRNA expression profiles in human testicular tissues of infertile men with different histopathologic patterns. Fertil Steril 2014; 101: 78–86 e2.CrossRefGoogle ScholarPubMed
Abu-Halima, M, Hammadeh, M, Schmitt, J, Leidinger, P, Keller, A, Meese, E et al. Altered microRNA expression profiles of human spermatozoa in patients with different spermatogenic impairments. Fertil Steril 2013; 99: 1,249–55 e16.CrossRefGoogle ScholarPubMed
Comazzetto, S, Di Giacomo, M, Rasmussen, KD, Much, C, Azzi, C, Perlas, E et al. Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci. PLoS Genet 2014; 10: e1004597.CrossRefGoogle ScholarPubMed
Bao, J, Li, D, Wang, L, Wu, J, Hu, Y, Wang, Z et al. MicroRNA-449 and microRNA-34b/c function redundantly in murine testes by targeting E2F transcription factor-retinoblastoma protein (E2F-pRb) pathway. J Biol Chem 2012; 287: 21,686–98.CrossRefGoogle ScholarPubMed
Smorag, L, Zheng, Y, Nolte, J, Zechner, U, Engel, W, Pantakani, DV. MicroRNA signature in various cell types of mouse spermatogenesis: Evidence for stage-specifically expressed miRNA-221, -203 and -34b-5p mediated spermatogenesis regulation. Biol Cell 2012; 104: 677–92.CrossRefGoogle ScholarPubMed
Bouhallier, F, Allioli, N, Lavial, F, Chalmel, F, Perrard, MH, Durand, P et al. Role of miR-34c microRNA in the late steps of spermatogenesis. RNA 2010; 16: 720–31.CrossRefGoogle ScholarPubMed
Liang, X, Zhou, D, Wei, C, Luo, H, Liu, J, Fu, R et al. MicroRNA-34c enhances murine male germ cell apoptosis through targeting ATF1. PLoS One 2012; 7: e33861.CrossRefGoogle ScholarPubMed
Martín-de-Lara, F, Sanchez-Aparicio, P, Arias de la Fuente, C, Rey-Campos, J. Biological effects of FoxJ2 over-expression. Transgenic Res 2008; 17: 1,131–41.CrossRefGoogle ScholarPubMed
Liu, WM, Pang, RT, Chiu, PC, Wong, BP, Lao, K, Lee, KF et al. Sperm-borne microRNA-34c is required for the first cleavage division in mouse. Proc Natl Acad Sci USA 2012; 109: 490–4.Google Scholar
Herati, A, Mielnik, A, Schlegel, P, Paduch, D. MP76–20 human sperm MIRNA profile in patients with normozoospermia and teratozoospermia. J Urol 2015; 193: e991.CrossRefGoogle Scholar
Buchold, GM, Coarfa, C, Kim, J, Milosavljevic, A, Gunaratne, PH, Matzuk, MM. Analysis of microRNA expression in the prepubertal testis. PloS One 2010; 5: e15317.CrossRefGoogle ScholarPubMed
Tong, MH, Mitchell, D, Evanoff, R, Griswold, MD. Expression of Mirlet7 family microRNAs in response to retinoic acid-induced spermatogonial differentiation in mice. Biol Reprod 2011; 85: 189–97.CrossRefGoogle ScholarPubMed
Wu, W, Hu, Z, Qin, Y, Dong, J, Dai, J, Lu, C et al. Seminal plasma microRNAs: Potential biomarkers for spermatogenesis status. Mol Hum Reprod 2012; 18: 489–97.CrossRefGoogle ScholarPubMed
Lienert, F, Wirbelauer, C, Som, I, Dean, A, Mohn, F, Schubeler, D. Identification of genetic elements that autonomously determine DNA methylation states. Nat Genet 2011; 43: 1,091–7.CrossRefGoogle ScholarPubMed
Deaton, AM, Bird, A. CpG islands and the regulation of transcription. Genes Dev 2011; 25: 1,010–22.CrossRefGoogle ScholarPubMed
Hajkova, P, Erhardt, S, Lane, N, Haaf, T, El-Maarri, O, Reik, W et al. Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 2002; 117: 15–23.CrossRefGoogle ScholarPubMed
Rajender, S, Avery, K, Agarwal, A. Epigenetics, spermatogenesis and male infertility. Mutat Res 2011; 727: 62–71.CrossRefGoogle ScholarPubMed
Boissonnas, CC, Jouannet, P, Jammes, H. Epigenetic disorders and male subfertility. Fertil Steril 2013; 99: 624–31.CrossRefGoogle ScholarPubMed
Reik, W, Dean, W, Walter, J. Epigenetic reprogramming in mammalian development. Science 2001; 293: 1,089–93.CrossRefGoogle ScholarPubMed
Kobayashi, H, Sato, A, Otsu, E, Hiura, H, Tomatsu, C, Utsunomiya, T et al. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet 2007; 16: 2,542–51.CrossRefGoogle ScholarPubMed
Marques, CJ, Francisco, T, Sousa, S, Carvalho, F, Barros, A, Sousa, M. Methylation defects of imprinted genes in human testicular spermatozoa. Fertil Steril 2010; 94: 585–94.CrossRefGoogle ScholarPubMed
Minor, A, Chow, V, Ma, S. Aberrant DNA methylation at imprinted genes in testicular sperm retrieved from men with obstructive azoospermia and undergoing vasectomy reversal. Reproduction 2011; 141: 749–57.CrossRefGoogle ScholarPubMed
Houshdaran, S, Cortessis, VK, Siegmund, K, Yang, A, Laird, PW, Sokol, RZ. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PloS One 2007; 2: e1289.CrossRefGoogle ScholarPubMed
Khazamipour, N, Noruzinia, M, Fatehmanesh, P, Keyhanee, M, Pujol, P. MTHFR promoter hypermethylation in testicular biopsies of patients with non-obstructive azoospermia: The role of epigenetics in male infertility. Hum Reprod 2009; 24: 2,361–4.CrossRefGoogle ScholarPubMed
Tunc, O, Tremellen, K. Oxidative DNA damage impairs global sperm DNA methylation in infertile men. J Assist Reprod Genet 2009; 26: 537–44.CrossRefGoogle ScholarPubMed
Navarro-Costa, P, Nogueira, P, Carvalho, M, Leal, F, Cordeiro, I, Calhaz-Jorge, C et al. Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm. Hum Reprod 2010; 25: 2,647–54.CrossRefGoogle ScholarPubMed
Nanassy, L, Carrell, DT. Abnormal methylation of the promoter of CREM is broadly associated with male factor infertility and poor sperm quality but is improved in sperm selected by density gradient centrifugation. Fertil Steril 2011; 95: 2,310–4.CrossRefGoogle ScholarPubMed
Ramasamy, R, Ridgeway, A, Lipshultz, LI, Lamb, DJ. Integrative DNA methylation and gene expression analysis identifies discoidin domain receptor 1 association with idiopathic nonobstructive azoospermia. Fertil Steril 2014; 102: 968–73 e3.CrossRefGoogle ScholarPubMed
Noma, K, Allis, CD, Grewal, SI. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 2001; 293: 1,150–5.CrossRefGoogle Scholar
Khalil, AM, Boyar, FZ, Driscoll, DJ. Dynamic histone modifications mark sex chromosome inactivation and reactivation during mammalian spermatogenesis. Proc Natl Acad Sci USA 2004; 101: 16,583–7.CrossRefGoogle ScholarPubMed
Hammoud, SS, Nix, DA, Zhang, H, Purwar, J, Carrell, DT, Cairns, BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature 2009; 460: 473–8.CrossRefGoogle ScholarPubMed
Aoki, VW, Liu, L, Jones, KP, Hatasaka, HH, Gibson, M, Peterson, CM et al. Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability. Fertil Steril 2006; 86: 1,408–15.CrossRefGoogle ScholarPubMed
Sadeghi-Nejad, H, Farrokhi, F. Genetics of azoospermia: Current knowledge, clinical implications, and future directions. Part II: Y chromosome microdeletions. Urol J 2007; 4: 192–206.Google ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×