Emerging evidence for the role of genomic instability in male factor infertility

Systems Biology in Reproductive Medicine

Volumn 58, Issue 2, 2012, Pages 71-80

  Aston, Kenneth I ^a   Carrell, Douglas T ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Chromosome instability; Copy number variation; Genomic instability; Male infertility; Microsatellite instability

Indexed keywords

ANEUPLOIDY; CHROMOSOMAL INSTABILITY; COPY NUMBER VARIATION; GENOMIC INSTABILITY; HEALTH STATUS; HUMAN; MALE INFERTILITY; MICROSATELLITE INSTABILITY; NEOPLASM; PRIORITY JOURNAL; REVIEW; SPERMATOGENESIS;

GENE DOSAGE; GENOMIC INSTABILITY; HUMANS; INFERTILITY, MALE; MALE; MICROSATELLITE INSTABILITY; SPERMATOZOA;

EID: 84858437194     PISSN: 19396368     EISSN: 19396368     Source Type: Journal    
DOI: 10.3109/19396368.2011.635751     Document Type: Review

References (110)

1. Aguilera, A. and Gomez-Gonzalez, B. (2008) Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet 9:204-217. (Pubitemid 351271797)
2. Aston, K.I., Carrell, D.T. (2009) Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl 30:711-725.
3. Aston, K.I., Krausz, C., Laface, I., Ruiz-Castane, E., Carrell, D.T. (2010) Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent. Hum Reprod. 25(6):1383-97.
4. Bacon, A.L., Dunlop, M.G., Farrington, S.M. (2001) Hypermutability at a poly(A/T) tract in the human germline. Nucleic Acids Res 29:4405-4413. (Pubitemid 33064781)
5. Baker, S.M., Bronner, C.E., Zhang, L., Plug, A.W., Robatzek, M., Warren, G., et al. (1995) Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82:309-319.
6. Baker, S.M., Plug, A.W., Prolla, T.A., Bronner, C.E., Harris, A.C., Yao, X., et al. (1996) Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet 13:336-342. (Pubitemid 26230500)
7. Boissonnas, C.C., Abdalaoui, H.E., Haelewyn, V., Fauque, P., Dupont, J.M., Gut, I., et al. (2010) Specific epigenetic alterations of IGF2-H19 locus in spermatozoa from infertile men. Eur J Hum Genet 18:73-80.
8. Brykczynska, U., Hisano, M., Erkek, S., Ramos, L., Oakeley, E.J., Roloff, T.C., et al. (2010) Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol. 17(6):679-87.
9. Chandley, A.C., Edmond, P., Christie, S., Gowans, L., Fletcher, J., Frackiewicz, A., et al. (1975) Cytogenetics and infertility in man. I. Karyotype and seminal analysis: results of a five-year survey of men attending a subfertility clinic. Ann Hum Genet 39:231-254.
10. Charames, G.S., Bapat, B. (2003) Genomic instability and cancer. Curr Mol Med 3:589-596. (Pubitemid 37236402)
11. de la Chapelle, A. (2003) Microsatellite instability. N Engl J Med 349:209-210.
12. de Vries, J.W., Hoffer, M.J., Repping, S., Hoovers, J.M., Leschot, N.J., van der Veen, F. (2002) Reduced copy number of DAZ genes in subfertile and infertile men. Fertil Steril 77:68-75. (Pubitemid 34093895)
13. Dohle, G.R., Colpi, G.M., Hargreave, T.B., Papp, G.K., Jungwirth, A., Weidner, W. (2005) EAU guidelines on male infertility. Eur Urol 48:703-711. (Pubitemid 41508883)
14. Dohle, G.R., Halley, D.J., Van Hemel, J.O., van den Ouwel, A.M., Pieters, M.H., Weber, R.F., et al. (2002) Genetic risk factors in infertile men with severe oligozoospermia and azoospermia. Hum Reprod 17:13-16. (Pubitemid 34130254)
15. Eshleman, J.R., Lang, E.Z., Bowerfind, G.K., Parsons, R., Vogelstein, B., Willson, J.K., et al. (1995) Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer. Onco-gene 10:33-37.
16. Faulkner, S.W., Friedlander, M.L. (2000) Microsatellite instability in germ cell tumors of the testis and ovary. Gynecol Oncol 79:38-43.
17. Feitsma, H., Leal, M.C., Moens, P.B., Cuppen, E., Schulz, R.W. (2007) Mlh1 deficiency in zebrafish results in male sterility and aneuploid as well as triploid progeny in females. Genetics 175:1561-1569. (Pubitemid 46789944)
18. Ferras, C., Zhou, X.L., Sousa, M., Lindblom, A., Barros, A. (2007) DNA mismatch repair gene hMLH3 variants in meiotic arrest. Fertil Steril 88:1681-1684. (Pubitemid 350216854)
19. Filipponi, D., Feil, R. (2009) Perturbation of genomic imprinting in oligozoospermia. Epigenetics 4:27-30.
20. Giachini, C., Laface, I., Guarducci, E., Balercia, G., Forti, G., Krausz, C. (2008) Partial AZFc deletions and duplications: clinical correlates in the Italian population. Hum Genet 124:399-410.
21. Giachini, C., Nuti, F., Turner, D.J., Laface, I., Xue, Y., Daguin, F., et al. (2009) TSPY1 copy number variation influences spermatogenesis and shows differences among Y lineages. J Clin Endocrinol Metab 94:4016-4022.
22. Giwercman, A., Richiardi, L., Kaijser, M., Ekbom, A., Akre, O. (2005) Reduced risk of prostate cancer in men who are childless as compared to those who have fathered a child: a population based case-control study. Int J Cancer 115:994-997. (Pubitemid 40791840)
23. Gohring, I., Blumlein, H.M., Hoyer, J., Ekici, A.B., Trautmann, U., Rauch, A. (2008) 6.7 Mb interstitial duplication in chromosome band 11q24.2q25 associated with infertility, minor dysmorphic features and normal psychomotor development. Eur J Med Genet 51:666-671.
24. Hammoud, S.S., Nix, D.A., Hammoud, A.O., Gibson, M., Cairns, B. R., Carrell, D.T. (2011) Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum Reprod.
25. Hammoud, S.S., Nix, D.A., Zhang, H., Purwar, J., Carrell, D.T., Cairns, B.R. (2009a) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460:473-478.
26. Hammoud, S.S., Purwar, J., Pflueger, C., Cairns, B.R., Carrell, D.T. (2009b) Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility. Fertil Steril 94 (5):1728-33.
27. Hansen, S., Eichler, E.E., Fullerton, S.M., Carrell, D. (2010) SPANX gene variation in fertile and infertile males. Syst Biol Reprod Med 55:18-26.
28. Honecker, F., Wermann, H., Mayer, F., Gillis, A.J., Stoop, H., van Gurp, R.J., et al. (2009) Microsatellite instability, mismatch repair deficiency, and BRAF mutation in treatment-resistant germ cell tumors. J Clin Oncol 27:2129-2136.
29. Hotaling, J.M., Walsh, T.J. (2009) Male infertility: a risk factor for testicular cancer. Nat Rev Urol 6:550-556.
30. Houshdaran, S., Cortessis, V.K., Siegmund, K., Yang, A., Laird, P.W., Sokol, R.Z. (2007) Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS One 2:e1289.
31. Huddart, R.A., Wooster, R., Horwich, A., Cooper, C.S. (1995) Micro-satellite instability in human testicular germ cell tumours. Br J Cancer 72:642-645.
32. Iguchi, N., Tobias, J.W., Hecht, N.B. (2006) Expression profiling reveals meiotic male germ cell mRNAs that are translationally up-and down-regulated. Proc Natl Acad Sci USA 103:7712-7717.
33. Jeffreys, A.J., Tamaki, K., MacLeod, A., Monckton, D.G., Neil, D.L., Armour, JA. (1994) Complex gene conversion events in germline mutation at human minisatellites. Nat Genet 6:136-145. (Pubitemid 24188593)
34. Jensen, T.K., Jacobsen, R, Christensen, K., Nielsen, N.C., Bostofte, E. (2009) Good semen quality and life expectancy: a cohort study of 43, 277 men. Am J Epidemiol 170:559-565.
35. Jobling, MA. (2008) Copy number variation on the human Y chromosome. Cytogenet Genome Res 123:253-262.
36. Jobling, M.A., Tyler-Smith, C. (2003) The human Y chromosome: an evolutionary marker comes of age. Nat Rev Genet 4:598-612. (Pubitemid 36917502)
37. Johansen, C.T., Wang, J., Lanktree, M.B., Cao, H., McIntyre, A.D., Ban, M.R., et al. (2010) Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet 42:684-687.
38. Jorgensen, K.T., Pedersen, B.V., Johansen, C, Frisch, M. (2008) Fatherhood status and prostate cancer risk. Cancer 112:919-923. (Pubitemid 351240586)
39. Jorgez, C.J., Weedin, J.W., Sahin, A., Tannour-Louet, M., Han, S., Bournat, J.C, et al. (2011) Aberrations in pseudoautosomal regions (PARs) found in infertile men with Y-chromosome micro-deletions. J Clin Endocrinol Metab 96:E674-679.
40. Kobayashi, H., Sato, A., Otsu, E., Hiura, H., Tomatsu, C, Utsuno-miya, T., et al. (2007) Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet 16:2542-2551. (Pubitemid 47617721)
41. Krausz, C, Chianese, C, Giachini, C, Guarducci, E., Laface, I., Forti, G (2011) The Y chromosome-linked copy number variations and male fertility. J Endocrinol Invest 34:376-382.
42. Krausz, C, Degl Innocenti, S. (2006) Y chromosome and male infertility: update, 2006. Front Biosci 11:3049-3061. (Pubitemid 43800396)
43. Krausz, C, Forti, G, McElreavey, K (2003) The Y chromosome and male fertility and infertility. Int J Androl 26:70-75. (Pubitemid 36408235)
44. Krausz, C, Giachini, C. (2007) Genetic risk factors in male infertility. Arch Androl 53:125-133. (Pubitemid 47035841)
45. Lee, C, Scherer, S.W. (2010) The clinical context of copy number variation in the human genome. Expert Rev Mol Med 12:e8.
46. Li, Z., Haines, C.J., Han, Y (2008) "Micro-deletions" of the human Y chromosome and their relationship with male infertility. J Genet Genomics 35:193-199. (Pubitemid 351611650)
47. Lin, Y.W., Hsu, L.C., Kuo, P.L., Huang, W.J., Chiang, H.S., Yeh, S.D., et al. (2007) Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan. Hum Mutat 28:486-494. (Pubitemid 46668607)
48. Lipkin, S.M., Moens, P.B., Wang, V., Lenzi, M., Shanmugarajah, D., Gilgeous, A., et al. (2002) Meiotic arrest and aneuploidy in MLH3-deficient mice. Nat Genet 31:385-390. (Pubitemid 35154447)
49. Maduro, M.R, Casella, R, Kim, E., Levy, N, Niederberger, C, Lipshultz, L.I., et al. (2003) Microsatellite instability and defects in mismatch repair proteins: a new aetiology for Sertoli cell-only syndrome. Mol Hum Reprod 9:61-68. (Pubitemid 36285145)
50. Marques, C.J., Carvalho, F., Sousa, M., Barros, A. (2004) Genomic imprinting in disruptive spermatogenesis. Lancet 363:1700-1702. (Pubitemid 38670329)
51. Marques, C.J., Costa, P., Vaz, B., Carvalho, F., Fernandes, S., Barros, A., et al. (2008) Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia. Mol Hum Reprod 14:67-74.
52. Martin, RH. (2008a) Cytogenetic determinants of male fertility. Hum Reprod Update 14:379-390. (Pubitemid 351858977)
53. Martin, RH. (2008b) Meiotic errors in human oogenesis and spermatogenesis. Reprod Biomed Online 16:523-531. (Pubitemid 351566167)
54. Mukherjee, S., Ridgeway, A.D., Lamb, D.J. (2010) DNA mismatch repair and infertility. Curr Opin Urol 20:525-532.
55. Nagvenkar, P., Desai, K., Hinduja, I., Zaveri, K. (2005) Chromosomal studies in infertile men with oligozoospermia & non-obstructive azoospermia. Indian J Med Res 122:34-42. (Pubitemid 41223494)
56. Nanassy, L., Carrell, D.T. (2011) 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 95:2310-2314.
57. Navarro-Costa, P., Nogueira, P., Carvalho, M., Leal, F., Cordeiro, I., Calhaz-Jorge, C., et al. (2010) Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm. Hum Reprod 25:2647-2654.
58. Negrini, S., Gorgoulis, V.G., Halazonetis, T.D. (2010) Genomic instability-an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11:220-228.
59. Neu, R.L., Barlow, M.J., Gardner, L.I. (1973) Communications and commentaries: A 46, XYq-male with aspermia. Fertil Steril 24:811-813.
60. Nickkholgh, B., Noordam, M.J., Hovingh, S.E., van Pelt, A.M., van der Veen, F., Repping, S. (2009) Y chromosome TSPY copy numbers and semen quality. Fertil Steril 94:1744-1747.
61. Nudell, D., Castillo, M., Turek, P.J., Pera, R.R. (2000) Increased frequency of mutations in DNA from infertile men with meiotic arrest. Hum Reprod 15:1289-1294. (Pubitemid 30335952)
62. Nuti, F., Krausz, C. (2008) Gene polymorphisms/mutations relevant to abnormal spermatogenesis. Reprod Biomed Online 16:504-513. (Pubitemid 351566165)
63. O'Flynn O'Brien, K.L., Varghese, A.C., Agarwal, A. (2010) The genetic causes of male factor infertility: a review. Fertil Steril 93:1-12.
64. Perrin, A., Basinko, A., Douet-Guilbert, N., Gueganic, N., Le Bris, M. J., Amice, V., et al. (2011) Aneuploidy and DNA fragmentation in sperm of carriers of a constitutional chromosomal abnormality. Cytogenet Genome Res 133:100-106.
65. Peschka, B., Leygraaf, J., Van der Ven, K., Montag, M., Schartmann, B., Schubert, R., et al. (1999) Type and frequency of chromosome aberrations in 781 couples undergoing intracytoplasmic sperm injection. Hum Reprod 14:2257-2263. (Pubitemid 29425410)
66. Pinto, D., Pagnamenta, A.T., Klei, L., Anney, R., Merico, D., Regan, R., et al. (2010) Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466:368-372.
67. Poplinski, A., Tuttelmann, F., Kanber, D., Horsthemke, B., Gromoll, J. (2010) Idiopathic male infertility is strongly associated with aberrant methylation of MEST and IGF2/H19 ICR1. Int J Androl. 33 (4):642-649.
68. Radpour, R., Gourabi, H., Dizaj, A.V., Holzgreve, W., Zhong, X.Y. (2008) Genetic investigations of CFTR mutations in congenital absence of vas deferens, uterus, and vagina as a cause of infertility. J Androl 29:506-513.
69. Repping, S., Skaletsky, H., Brown, L., van Daalen, S.K., Korver, C.M., Pyntikova, T., et al. (2003) Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection. Nat Genet 35:247-251. (Pubitemid 37363178)
70. Repping, S., Skaletsky, H., Lange, J., Silber, S., Van Der Veen, F., Oates, R.D., et al. (2002) Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure. Am J Hum Genet 71:906-922. (Pubitemid 135750521)
71. Retief, A.E., Van Zyl, J.A., Menkveld, R., Fox, M.F., Kotze, G.M., Brusnicky, J. (1984) Chromosome studies in 496 infertile males with a sperm count below 10 million/ml. Hum Genet 66:162-164. (Pubitemid 14142454)
72. Ruhayel, Y., Giwercman, A., Ulmert, D., Rylander, L., Bjartell, A., Manjer, J., et al. (2010) Male infertility and prostate cancer risk: a nested case-control study. Cancer Causes Control. 2010 Oct;21 (10):1635-43.
73. Salonia, A., Matloob, R., Gallina, A., Abdollah, F., Sacca, A., Briganti, A., et al. (2009) Are Infertile Men Less Healthy than Fertile Men? Results of a Prospective Case-Control Survey. Eur Urol. 56 (6):1025-1031
74. Sanderson, M.L., Hassold, T.J., Carrell, D.T. (2008) Proteins involved in meiotic recombination: a role in male infertility? Syst Biol Reprod Med 54:57-74.
75. Sato, A., Hiura, H., Okae, H., Miyauchi, N., Abe, Y., Utsunomiya, T., et al. (2011) Assessing loss of imprint methylation in sperm from subfertile men using novel methylation polymerase chain reaction Luminex analysis. Fertil Steril 95(1):129-34.
76. Schultz, N., Hamra, F.K., Garbers, D.L. (2003) A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. Proc Natl Acad Sci USA 100:12201-12206. (Pubitemid 37271538)
77. Sharpe, R.M., Skakkebaek, N.E. (1993) Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet 341:1392-1395. (Pubitemid 23159997)
78. Skakkebaek, N.E., Rajpert-De Meyts, E., Main, K.M. (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16:972-978. (Pubitemid 32451837)
79. Skaletsky, H., Kuroda-Kawaguchi, T., Minx, P.J., Cordum, H.S., Hillier, L., Brown, L.G., et al. (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423:825-837. (Pubitemid 36781267)
80. Stankiewicz, P., Lupski, J.R. (2010) Structural variation in the human genome and its role in disease. Annu Rev Med 61:437-455.
81. Stefansson, H., Rujescu, D., Cichon, S., Pietilainen, O.P., Ingason, A., Steinberg, S., et al. (2008) Large recurrent microdeletions associated with schizophrenia. Nature 455:232-236.
82. Tamowski, S., Aston, K.I., Carrell, D.T. (2010) The use of transgenic mouse models in the study of male infertility. Syst Biol Reprod Med 56:260-273.
83. Tempest, H.G. (2011) Meiotic recombination errors, the origin of sperm aneuploidy and clinical recommendations. Syst Biol Reprod Med 57:93-101.
84. Terribas, E., Bonache, S., Garcia-Arevalo, M., Sanchez, J., Franco, E., Bassas, L., et al. (2010) Changes in the expression profile of the meiosis-involved mismatch repair genes in impaired human sper-matogenesis. J Androl 31:346-357.
85. Thompson, S.L., Bakhoum, S.F., Compton, D.A. (2010) Mechanisms of chromosomal instability. Curr Biol 20:R285-295.
86. Tiepolo, L., Zuffardi, O. (1976) Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 34:119-124.
87. Tomasini, R., Tsuchihara, K., Wilhelm, M., Fujitani, M., Rufini, A., Cheung, C.C., et al. (2008) TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev 22:2677-2691.
88. Tuttelmann, F., Rajpert-De Meyts, E., Nieschlag, E., Simoni, M. (2007) Gene polymorphisms and male infertility-a meta-analysis and literature review. Reprod Biomed Online 15:643-658. (Pubitemid 350285979)
89. Tuttelmann, F., Simoni, M., Kliesch, S., Ledig, S., Dworniczak, B., Wieacker, P., et al. (2011) Copy number variants in patients with severe oligozoospermia and sertoli-cell-only syndrome. PLoS One 6:e19426.
90. Veigl, M.L., Kasturi, L., Olechnowicz, J., Ma, A.H., Lutterbaugh, J.D., Periyasamy, S., et al. (1998) Biallelic inactivation of hMLH1 by epi-genetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci USA 95:8698-8702. (Pubitemid 28350551)
91. Velasco, A., Corvalan, A., Wistuba, II, Riquelme, E., Chuaqui, R., Majerson, A., et al. (2008) Mismatch repair expression in testicular cancer predicts recurrence and survival. Int J Cancer 122:1774-1777. (Pubitemid 351413423)
92. Velasco, A., Riquelme, E., Schultz, M., Wistuba, II, Villarroel, L., Koh, M.S., et al. (2004) Microsatellite instability and loss of heterozygos-ity have distinct prognostic value for testicular germ cell tumor recurrence. Cancer Biol Ther 3:1152-1158; discussion 1159-1161. (Pubitemid 41350999)
93. Vincent, M.C., Daudin, M., De, M.P., Massat, G., Mieusset, R., Pon-tonnier, F., et al. (2002) Cytogenetic investigations of infertile men with low sperm counts: a 25-year experience. J Androl 23:18-22; discussion 44-45. (Pubitemid 34001124)
94. Visser, L., Westerveld, G.H., Korver, C.M., van Daalen, S.K., Hovingh, S.E., Rozen, S., et al. (2009) Y chromosome gr/gr deletions are a risk factor for low semen quality. Hum Reprod 24:2667-2673.
95. Vodicka, R., Vrtel, R., Dusek, L., Singh, A.R., Krizova, K., Svacinova, V., et al. (2007) TSPY gene copy number as a potential new risk factor for male infertility. Reprod Biomed Online 14:579-587.
96. Vogt, P.H. (2004) Genomic heterogeneity and instability of the AZF locus on the human Y chromosome. Mol Cell Endocrinol 224:1-9. (Pubitemid 39194620)
97. Vogt, P.H., Edelmann, A., Kirsch, S., Henegariu, O., Hirschmann, P., Kiesewetter, F., et al. (1996) Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet 5:933-943. (Pubitemid 26232272)
98. Walsh, T., McClellan, J.M., McCarthy, S.E., Addington, A.M., Pierce, S.B., Cooper, G.M., et al. (2008a) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320:539-543. (Pubitemid 351590668)
99. Walsh, T.J., Croughan, M.S., Schembri, M., Smith, J.F., Chan, J.M., Turek, P.J. (2008b) Infertile men may have increased risk for non-germ cell cancers: data from 51, 318 infertile couples. J Urol 179:654.
100. Walsh, T.J., Pera, R.R., Turek, P.J. (2009) The genetics of male infertility. Semin Reprod Med 27:124-136.
101. Walsh, T.J., Schembri, M., Turek, P.J., Chan, J.M., Carroll, P.R., Smith, J.F., et al. (2010) Increased risk of high-grade prostate cancer among infertile men. Cancer 116:2140-2147.
102. Wei, K., Clark, A.B., Wong, E., Kane, M.F., Mazur, D.J., Parris, T., et al. (2003) Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility. Genes Dev 17:603-614. (Pubitemid 36307545)
103. Wohlfahrt-Veje, C., Main, K.M., Skakkebaek, N.E. (2009) Testicular dysgenesis syndrome: foetal origin of adult reproductive problems. Clin Endocrinol (Oxf) 71:459-465.
104. Wong, E.C., Ferguson, K.A., Chow, V., Ma, S. (2008) Sperm aneuploi-dy and meiotic sex chromosome configurations in an infertile XYY male. Hum Reprod 23:374-378. (Pubitemid 351651254)
105. Writzl, K., Zorn, B., Peterlin, B. (2005) Copy number of DAZ genes in infertile men. Fertil Steril 84:1522-1525. (Pubitemid 41571913)
106. Xu, K., Lu, T., Zhou, H., Bai, L., Xiang, Y. (2010) The role of MSH5 C85T and MLH3 C2531T polymorphisms in the risk of male infertility with azoospermia or severe oligozoospermia. Clin Chim Acta 411:49-52.
107. Yang, Y., Ma, M., Li, L., Su, D., Chen, P., Ma, Y., et al. (2010) Differential effect of specific gr/gr deletion subtypes on sperma-togenesis in the Chinese Han population. Int J Androl 33:745-754.
108. Yatsenko, A.N., Iwamori, N., Iwamori, T., Matzuk, M.M. (2010) The power of mouse genetics to study spermatogenesis. J Androl 31:34-44.
109. Yong, E.L., Loy, C.J., Sim, K.S. (2003) Androgen receptor gene and male infertility. Hum Reprod Update 9:1-7. (Pubitemid 36305579)
110. Zhou, D., Xia, Y., Li, Y., Song, L., Hu, F., Lu, C., et al. (2011) Higher proportion of haploid round spermatids and spermatogenic disomy rate in relation to idiopathic male infertility. Urology 77:77-82.