The Genetics of Male Infertility

  • S. Bhasin
  • W. E. Taylor
  • C. Mallidis
  • B. Salehian
  • I. Sinha
  • M. Limbo
  • K. Ma
Part of the Mineralogical Society Series book series (ENDO, volume 5)


While a multitude of acquired causes can impair spermatogenesis, there is reason to believe that a genetic basis exists in a majority of infertile men (Bhasin et al, 1994; De Kretser et al, 1972; Lamb and Niederberger, 1994; Jaffe and Oates, 1994; Skakkebaek et al, 1994). The occurrence of these genetic defects in infertile men has significant implications for assisted reproductive technologies, particularly intracytoplasmic sperm injection (ICSI) (Bhasin et al, 1994). Because intracytoplasmic sperm injection may allow partners of these infertile men to become pregnant, it is possible that these genetic defects may be transmitted to the male offspring. This raises issues of informed consent and ethical concerns. Similarly, the widespread use of assisted reproductive techniques to induce pregnancy may result in accumulation of genetic defects in the population; these defects would have been otherwise weeded out because of infertility. Substantial prevalence of Y deletions and other known and unknown genetic defects in infertile men and the potential risk of transmitting this genetic disorder to their offspring provide a compelling rationale for genetic screening of infertile men prior to ICSI. The couples undergoing ICSI should be counseled about the potential risk of transmitting this genetic disorder to the offspring. Long term monitoring of ICSI babies for genetic disorders including Y deletions is warranted.


Germ Cell Follicle Stimulate Hormone Sertoli Cell Seminiferous Tubule Male Infertility 
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  1. Abbasi AA, Prasad AS, Ortega J, Congco J, Oberleas D. Gonadal function abnormalities in sicke cell anemia. Studies in adult male patients. Ann Intern Med 1976;85:601–5.PubMedGoogle Scholar
  2. Aguiano A, Oates RD, Amos JA, et al. Congenital bilateral absence of the vas deferens: a primarily genital form of cystic fibrosis. JAMA 1992;267:1794–98.CrossRefGoogle Scholar
  3. Ahmad K. The transmission of fragmented chromosomes in Drosophila melanogaster. Genetics. 1998;148:775–792.PubMedGoogle Scholar
  4. Albanese C, Colin IM, Crowley WF, Ito M, Pestell RG, Weiss J, Jameson JL. The gonadotropin genes: evolution of distinct mechanisms for hormonal control. Rec Prog Horm Res 1996;51:23–58.PubMedGoogle Scholar
  5. Baker J, Hardy MP, Zhou J, et al. Effects of an IGf1 gene null mutation on mouse reproduction. Mol Endocrinol 1996;10:903–918.PubMedCrossRefGoogle Scholar
  6. Baker SM, Plug AW, Prolla TA, et al. Involvement of mouse Mlhl in DNA mismatch repair and meiotic crossing over. Nat Genet 1996;13(3):336–342.PubMedCrossRefGoogle Scholar
  7. Bandmann HJ, Breit R, Perwine E (eds) Klinefelter’s Syndrome, New York, Springer Verlag, 1984.Google Scholar
  8. Bartke A, Naar EM, Johnson L, et al. Effects of expression of human or bovine growth hormone genes on sperm production and male reproductive performance in four lines of transgenic mice. J Reprod Fertil 1992;95:109–115.PubMedGoogle Scholar
  9. Beck ARP, Miller IJ, Anderson P, Steuli M. RNA binding protein TIAR essential for primordial germ cell development. Proc Natl Acad Sci USA 1998;95:2331–2336.PubMedCrossRefGoogle Scholar
  10. Beermann W, Hess O, and Meyer GF. Lampbrush Y chromosomes in spermiogenesis of Drosophila. In: Wolff, E. (ed) The relationship between experimental embryology and molecular biology. Gordon & Breach Science, New York, 1967;pp 61–81.Google Scholar
  11. Bennett WI, Gall A.M., Southard J.L, Sidman R.L. Abnormal spermiogenesis in quaking, a myelin deficient mutant mouse. Biol Reprod 1971;5: 30–58.PubMedGoogle Scholar
  12. Bhasin S, De Kretser DM, Baker HWG. Pathophysiology and natural history of male factor infertility. J Clin Endocrinol Metab 1994;79:1525–1529.PubMedCrossRefGoogle Scholar
  13. Bhat KM. The GAGA factor is required in the early Drosophila embryo not only for transcriptional regulation but also for nuclear division. Development. 1996;122:1113–1124.PubMedGoogle Scholar
  14. Bick D, Brunella F, Sherins RJ, et al. Brief report: intragenic deletion of the kalig-1 gene in Kallmann’s syndrome. N Engl J Med 1992;326:1752.PubMedGoogle Scholar
  15. Bonaccorsi.
    S, Pisano C, Puoti F, and Gatti M. Y chromosome loops in Drosophila melanogaster. Genetics 1988;120:1015–1034.Google Scholar
  16. Bridges CB. Non-disjunction as proof of the chromosome theory of heredity. Genetics 1916;1:1–52.PubMedGoogle Scholar
  17. Brousseau GE. Genetic analysis of the male fertility factors on the Y chromosome of Drosophila melanogaster. Genetics 1960;44:257–274.Google Scholar
  18. Bruère, A. N., Marshall, R.B. and Ward, D.P.J. Testicular hypoplasia and XXY sex chromosome complement in two rams: the ovine counterpart of Klinefelter’s syndrome in man. J. Reprod. Fert. 1969;19:103–108.Google Scholar
  19. Cassidy SB, Schwartz S. Prader-Willi and Angelman syndromes. Disorders of genomic imprinitng. Medicine 1998;77:140–51.PubMedCrossRefGoogle Scholar
  20. Castrillion DH, Gonczy P, Alexander S, et al. Toward a genetic analysis of spermatogenesis in Drosophila melanogaster: characterization of male-sterile mutants generated by single P element mutagenesis. Genetics 1993;135:489–505.Google Scholar
  21. Cattanach, B.M. (1961). XXY mice. Genet. Res. 2:156–160.CrossRefGoogle Scholar
  22. Centerwell, W.R. and Benirschke, K. Male tortoiseshell and calico (TC) cats: animal models of sex chromosome mosaics, aneuploids, polyploids and chimaeras. J. Hered. 1973;64:272–278.Google Scholar
  23. Chandley, A.C. (1979). The chromosomal basis of human infertility. Br. Med. Bull. 1979; 35: 181–186.PubMedGoogle Scholar
  24. Chaves-Carballo E, Hayles AB. Ullrich-Turner syndrome in the male: review of literature and report of a case with lymphocytic thyroiditis. Mayo Clin Proc 1966;41:843–47.PubMedGoogle Scholar
  25. Clermont Y. Dynamics of human spermatogenesis. In: Rosemberg, E., Paulsen, C.A. (eds) The Human Testis. Plenum Press, New York London, pp 47–61, 1970.Google Scholar
  26. Clough, E., Pyle, R.L., Hare, W.C.D., Kelly, D.F. and Patterson, D.F. XXY sex chromosome constitution in a dog with testicular hypoplasia and congenital heart disease. Cytogenetics 1970; 9:71–77.PubMedGoogle Scholar
  27. Cohen PE, Hardy MP, Pollard JW. Colony-stimulating factor-1 plays a major role in the development of reproductive function in male mice. Mol Endocrinol 1997;11:1636–1650.PubMedCrossRefGoogle Scholar
  28. Conway GS. Clinical manifestations of genetic defects affecting gonadotropins and their receptors. Clin Endocrinol 1996;45:657–63.CrossRefGoogle Scholar
  29. Cooke HJ et al. A murine homolog of the human DAZ gene is autosomal and expressed only in male and female gonads. Hum Mol Genet 1996;5:513–516PubMedCrossRefGoogle Scholar
  30. Crowley WF, Whitcomb RW, Jameson JL, et al. Neuroendocrine control of human reproduction in the male. Rec Prog Horm Res 1991;47:27–67.PubMedGoogle Scholar
  31. Dada OA, Nduka EU. Endocrine function and hemoglobinopathies: relation between the sickle cell gene and circulating plasma levels of testosterone, LH, and FSH in adult males. Clin Chim Acta 1980;105:269–273.PubMedCrossRefGoogle Scholar
  32. Davidoff F, Federman DD. Mixed gonadal dysgenesis. Pediatrics 1973;52:725–32.PubMedGoogle Scholar
  33. de Boer, P. (1976). Chromosomal causes for fertility reduction in mammals. In: de Serres FJ (ed) Chemical Mutagens, vol 10. Plenum, New York, pp 427–467.Google Scholar
  34. de Boer, P, Searle, AG, van der Hoeven FA, de Rooij, DG and Beechey CV Male pachytene pairing in single and double translocation heterozygotes and spermatogenic impairment in the mouse. Chromosoma (Berl) 1986;93: 326–336.CrossRefGoogle Scholar
  35. De Kretser DM, Burger HGG, Fortune D, et al. Hormonal, histological, and chromosomal studies in adult males with testicular disorders. J Clin Endocrinol Metab 1972;35:392–401.PubMedGoogle Scholar
  36. De Roux N, Young J, Misrahi M, Genet R, Chanson P, Schaison G, Milgrom E. A family with hypogonadotropic and mutations in the GnRH receptor. N Engl J Med 1997;337:1597–1602.PubMedCrossRefGoogle Scholar
  37. DeSanctis V, Vullo C, Katz M, et al. Induction of spermatogenesis in thalessemia. Fertil Steril 1988;50:969–975, 1988.Google Scholar
  38. Ding D. Mitochondrially encoded 16S large ribosomal RNA is concentrated in the posterior polar plasma of early Drosophila embryos, but is not required for pole cell formation. Dev Biol 1994;163:593–515.CrossRefGoogle Scholar
  39. Dix DJ, Allen JW, Collins BW, et al. Targeted gene disruption of Hsp 70-2 results in failed meiosis, germ cell apoptosis, and male infertility. Proc Natl Acad Sci USA 1996;93: 324–3268.CrossRefGoogle Scholar
  40. Dooher, G.B. and Bennett, D. Abnormal microtubular systems in mouse spermatids associated with a mutant gene at the T-locus. J. Embryol. Exp. Morph. 1974; 32: 749–761.PubMedGoogle Scholar
  41. Eberhardt CG, Maines JZ, Wasserman SA. Meiotic cell cycle requirement for a fly homolog of human Deleted in Azoospermia. Nature 1996; 381:783–785.CrossRefGoogle Scholar
  42. Eddy EM, Washburn TF, Bunch DO, et al. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 1996; 137: 4796–4805.PubMedCrossRefGoogle Scholar
  43. Eicher EM, Hale DW, Hunt PA, Lee BK, Tucker PK, King TR, Eppig JT and Washburn LL. The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region. Cytogenet. Cell Genet. 1991; 57: 221–230.Google Scholar
  44. Erdelyi M. Genetic and developmental analysis of mutant Ketel alleles that identify the Drosophila important-beta homologue. Acta Biol Hung 1997;48:323–338.PubMedGoogle Scholar
  45. Fryns JP, Kleckowska A and van den Berghe H. The X Chromosome and Sexual Development: Clinical Aspects. Alan R. Liss, Inc., 150 Fifth Avenue, New York, NY 10011 pp. 115–126, 1983.Google Scholar
  46. Godin I, Deed R, Cooke J, et al. Effects of the steel gene product on mouse primordial germ cells in culture. Nature 1991;352:807–9.PubMedCrossRefGoogle Scholar
  47. Gordon DL, Krempotic E, Thomas W, et al. Pathologic testicular findings in Klinefelter’s syndrome. Arch Intern Med 1972;130:726–730.PubMedCrossRefGoogle Scholar
  48. Griswold, M.D. (1988). Protein secretions of Sertoli cells. Int Rev Cytol 1988; 110:133–156.PubMedGoogle Scholar
  49. Gunay-Aygun M, Cassidy SB, Nicholls RD. Prader-Willi and other syndromes associated with obesity and mental retardation. Behav Genet 1997;27:307–24.PubMedCrossRefGoogle Scholar
  50. Hagaman JR, Moyer JS, Bachman ES, et al. Angiotensin-converting enzyme and male fertility. Proc Natl Acad Sci USA 1998; 95: 2552–2557.PubMedCrossRefGoogle Scholar
  51. Hamerton, J.L., Canning, N., Ray, M. and Smith, S. (1975). A cytogenetic survey of 14069 newborn infants. I. Incidence of chromosome abnormalities. Clin. Genet. 1975; 8: 223–243.PubMedGoogle Scholar
  52. Handel MA. Genetic control of spermatogenesis in mice. In: Results and problems in cell differentiation. Spermatogenesis: genetics aspects. ed. by W. Hennig, pp 1–62. Berli: Springer-Verlag, pp 1–62, 1987.Google Scholar
  53. Hardy RW, Lindsley DL, Livak KJ, Lewis B, Silverstein AL, Joslyn GL, Edwards J and Bonaccorsi S. Cytogenetic analysis of a segment of the Y chromosome of Drosophila melanogaster. Genetics 1984;107:591–610.PubMedGoogle Scholar
  54. Hekman ACP, Trapman J, Mulder AH, Van Gaalen JLM, Zwarthoff EC. Interferon expression in the testes of transgenic mice leads to sterility. J Biol Chem 1988;263:12151–12155.PubMedGoogle Scholar
  55. Heller CG, and Clermont Y. Kinetics of the germinal epithelium in man. Rec Prog Horm Res 1964; 20:545–75.PubMedGoogle Scholar
  56. Henagariu O, Hirschmann P, Kilian K., et al. Rapid screening of the Y chromosome in idiopathic sterile men, diagnostic for deletions in AZF, a genetic Y factor, expressed during spermatogenesis. Andrologia 1994;26:97–106.Google Scholar
  57. Hendy JA, Kaestner KH, Weinbauer GF, et al. Severe impairment of spermatogenesis in mice lacking the CREM gene. Nature 1996; 380: 162–165.CrossRefGoogle Scholar
  58. Hennig W (ed). Results and problems in cell differentiation. Spermatogenesis: genetic aspects. Berlin: Springer-Verlag, 1987;15:V.Google Scholar
  59. Hess O and Meyer GF. Genetic activities of the Y chromosome in Drosophila during spermatogenesis. Adv Genet 1968;14:171–223.PubMedCrossRefGoogle Scholar
  60. Hess O. Genetic function correlated with unfolding of lampbrush loops by the Y chromosome in spermatocytes of Drosophila hydei. Mol. Gen. Genet. 1970; 106:328–346.PubMedCrossRefGoogle Scholar
  61. Hollander WF. Hydrocephalic-polydactyl, a recessive and pleiotropic mutant in the mouse, and its location in Chromosome 6. Iowa Res 1976; 51:13–23.Google Scholar
  62. Horowitz TW. The Drosophila Pipsqueak Gene Encodes a Nuclear BTB-Domain-Containing Protien Required Early in Oogenesis. Development. 1996; 122: 1859–1871.PubMedGoogle Scholar
  63. Hsieh-Li HM, Witte DP, Weinstein M, et al. Hoxa 11 structure extensive antisense transcription, and function in male and female infertility. Development 1995;121:1373–1385.PubMedGoogle Scholar
  64. Huang LS, Voyiaziakis E, Chen HL, et al. A novel functional role for apolipoprotein B in male infertility in heterozygous apolipoprotein. Proc Natl Acad Sci USA 1996; 93: 10903–10907.PubMedCrossRefGoogle Scholar
  65. Huckins C, Bullock LP and Long JL (1981). Morphological profiles of cryptorchid XXY mouse testes. Anat. Rec. 1981; 199: 507–518.PubMedCrossRefGoogle Scholar
  66. Hulsebos TJM, Hackstein JHP and Hennig W. Lampbrush loop specific protein of Drosophila hydei. Proc Nat Acad Sci USA 1984;81:3404–3408.PubMedCrossRefGoogle Scholar
  67. Ivett, J.L., Tice, R.R. and Bender, M.A. (1978). Y two X’s? An XXY genotype in Chinese hamster, C. griseus. J Hered 1978; 69: 128–129.PubMedGoogle Scholar
  68. Jacobs PA, Melville M, Ratcliffe S, Keay S and Syme J. A cytogenetic survey of 11680 newborn infants. Ann. Hum. Genet 1974; 37: 359–376.PubMedGoogle Scholar
  69. Jaffe T, Oates RD. Genetic abnormalities and reproductive failure. Urol Clin North Am 1994;21:389–408.PubMedGoogle Scholar
  70. Jameson JL. Inherited disorders of the gonadotropin hormones. Mol Cell Endocrinol 1996;125:143–9.PubMedCrossRefGoogle Scholar
  71. Johnson DR and Hunt DM. Hop-sterile, a mutant gene affecting sperm tail development in the mouse. J Embryol Exp Morphol 1971; 25: 223–236.PubMedGoogle Scholar
  72. Kastner P, Mark M, Leid M, et al. Abnormal spermatogenesis in RXR beta mutant mice. Genes Dev. 1996; 10: 80–92.PubMedGoogle Scholar
  73. Keyes LN. The Drosophila gene fs(2) cup interacts with out to define a cytoplasmic pathway required for the structure and function of germline chromosomes. Development 1996;124:1419–1431.Google Scholar
  74. Kiefer BI. Ultrastructural abnormalities in developing sperm of X/O Drosophila melanogaster. Genetics 1966;54:1441–1452.PubMedGoogle Scholar
  75. Kjessler, B. Karyotype, meiosis and spermatogenesis in a sample of men attending an infertility clinic. in Monographs in Human Genetics, Vol. 2. S. Karger (Basel and New York), 1966.Google Scholar
  76. Kletzky OA, Costin G, Marrs RP, et al. Gonadotropin insufficiency in patients with thalessemia major. J Clin Endocrinol Metab 1979; 48:901–5.PubMedGoogle Scholar
  77. Knudson CM, Tung KS, Tourtellotte WG, et al. Bax-deficient mice with lymphoid hyperplasia and male germ cell death. Science 1995; 270: 96–99.PubMedCrossRefGoogle Scholar
  78. Koulischer L, Schoysman R. Etudes des chromosomes mitotiques et méiotiques chez les hommes infertiles. J Génét Hum 1975; 23:50–70.Google Scholar
  79. Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle-stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet 1997; 15:201–204.PubMedCrossRefGoogle Scholar
  80. Lamb DJ, Niederberger CS. Animal models that mimic human male reproductive defects. Urol Clinics North Am 1994;21:377–87.Google Scholar
  81. Landfeld SC, Schambelan M, Kaplan SL, et al. Clomiphene responsive hypogonadism in sickle cell anemia. Ann Intern Med 9 1993; 9:480–3.Google Scholar
  82. LaSalle JM, Ritchie RJ, Glatt H, Lalande M. Clonal heterogenieety at allelic methylation sites diagnostic for Prader-Willi and Angelman syndromes. Proc Natl Acad Sci USA. 1998;95:1675–80.PubMedCrossRefGoogle Scholar
  83. Latronico AC, Anasti J, Arnhold IJ, Rapaport R, Mendonca BB, Bloise W, Castro M, Tsigos C, Chrousos GP. Brief-report: testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the LH receptor gene. N Engl J Med 1996;334:507–512.PubMedCrossRefGoogle Scholar
  84. Laue L, Wu SM, Kudo M, Hsueh AJ, Cutler GB, Jr., Griffin JE, Wilson JD, Brain C, berry AC, Grant DB, et al. A nonsense mutation of the human luteinizing hormone receptor gene in Leydig cell hypoplasia. Hum Mol Genet 1995;4:1429–1433.PubMedCrossRefGoogle Scholar
  85. Laue LL, Wu SM, Kudo M, Bourdony CJ, Cutler CJ, Hsueh AJ, Chan WY. Compound heterozygous mutations of the luteinizing hormone receptor gene in Leydig cell hypoplasia. Mol Endocrinol 1996; 10:987–997.PubMedCrossRefGoogle Scholar
  86. Layman LC, Cohen DP, Jin M, Xie J, Li Z, Reindollar RH, Bolbolan S, Bick DP, Sherins RR, Duck LW, Musgrove LC, Sellers JC, Neill JD. Mutations in GnRH receptor gene cause hypogonadotropic hypogonadism. Nat Genet 1998; 18:14–5.PubMedCrossRefGoogle Scholar
  87. Layman LC, Lee E-J, Peak DB, Namnoum AB, Vu KV, van Lingen BL, Gray ML, McDonough PG, Reindollar RH, Jamesom JL. Delayed puberty and hypogonadism caused by mutations in the follicle-stimulating hormone beta subunit gene. N Engl J Med 1997;337:607–611.PubMedCrossRefGoogle Scholar
  88. Layman LC, Peak DB, Xie J, Sohn SH, Reinholder RH, Gray MR. Mutation analysis of the GnRH receptor gene in idiopathic hypogonadotropic hypogonadism. Fertil Steril 1997;68:1079–1085.PubMedCrossRefGoogle Scholar
  89. Lee YH, Sauer BH, Gonzalez FJ. Laron dwarfism and non-insulin dependent diabetes mellitus in the Hnf-1 alpha knockout mouse. Mol Cell Biol 1998; 18:3059–3068PubMedGoogle Scholar
  90. Legouis R, Hardelin J-P, Levilliers J, et al. The candidate gene for the X-linked Kallmann’s syndrome encodes a protein related to adhesion molecules. Cell 1991;87:423–35.CrossRefGoogle Scholar
  91. Lewis SE, Turchin HA and Wojitowicz TE. Fertility studies of complementing genotypes at the albino locus of the mouse. J Reprod Fertil 1978; 53: 197–202.PubMedGoogle Scholar
  92. Li K, Xy EY, Ceal JK, Turner FR, Megraw TL, Kaufman TC. Drosophila centrosim protein is required for male meiosis and assembly of the flagellar axoneme. J Cell Biol 1998;141:455–467.PubMedCrossRefGoogle Scholar
  93. Lifschytz E and Meyer GF. Characterization of male meiotic sterile mutations in Drosophila melanogaster. The genetic control of meiotic divisions and gametogenesis. Chromosoma (Berl) 1977;64:371–392.Google Scholar
  94. Lifschytz E and Hareven D. Gene expression and the control of spermatid morphogenesis in Drosophila melanogaster. Dev Biol 1977;58:276–294.PubMedCrossRefGoogle Scholar
  95. Lin TY, Viswanathan S, Wood C, Wilson PG, Wolf N, Fuller MT. Coordinate development control of meiotic cell cycle and spermatid differentiation in Drosophila Males. Development. 1996; 122: 1331–1341.PubMedGoogle Scholar
  96. Lindsley DL, and Lifschytz E. The genetic control of spermatogenesis in Drosophila. In: Beatty RA, Gluecksohn-Waelsch S (eds) The genetics of the spermatozoon. Proc. Int. Symp. Edinburgh, pp 203–222, 1972.Google Scholar
  97. Lindsley DL, and Tokuyasu KT. Spermatogenesis. In: Ashburner M, Wright TRF (eds) The genetics and biology of Drosophila, vol 2d. Academic Press, London, pp 225–294, 1980.Google Scholar
  98. Luoh SW, Bain PA, Polakiewicz RD, Goodheart ML, et al. Zfx mutation results in small animal size and reduced germ cell number in male and female mice. Development 1997; 124: 2275–2284.PubMedGoogle Scholar
  99. Lyon MF, Searle AG, Ford CE, and Ohno S. A mouse translocation suppressing sex-linked variegation. Cytogenet 1964;3:306–323.Google Scholar
  100. Lyon MF and Meredith R. Autosomal translocations causing male sterility and viable aneuploidy in the mouse. Cytogenet 1966; 5: 335–354.Google Scholar
  101. Lyon, M.F. The t-complex and the genetical control of development. Symp Zool Soc Lond 1981; 47: 455–477.Google Scholar
  102. Ma K, Inglis JD, Sharkey A, et al. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 1993;75:1287–1295.PubMedCrossRefGoogle Scholar
  103. Ma K, Sharkey A, Kirsh S, et al. Towards the molecular localization of the AZF locus: mapping of microdeletions in azoopermic men within fourteen subintervals of interval 6 of the human Y-chromosome. Hum Mol Genet 1992; 1:29–33.PubMedCrossRefGoogle Scholar
  104. Magram J, Bishop JM. Dominant male sterility in mice caused by insertion of a transgene. Proc Natl Acad Sci USA 1991;88:10327–32.PubMedCrossRefGoogle Scholar
  105. Mastrogiacomo I, Pagani E, Novelli G, Angelini C, Gennerelli M, Menegazzo G, Dallapiccolo B. Male hypogonadism is related to CTG in triplet mutation. J Endocrinol Invest 1994;17:181–3.Google Scholar
  106. McLaren A, Simpson E, Epplen JT, et al. Location of the gene controlling HY antigen expression and testis determination on the mouse Y chromosome. Proc Natl Acad Sci USA 1988; 85: 6442–6445.PubMedCrossRefGoogle Scholar
  107. Mibikay M, Tadros H, Ishida N, et al. Impaired fertility in mice deficient for the testicular germ cell protease PC4. Proc Natl Accad Sci USA 1997; 94: 6842–6846.CrossRefGoogle Scholar
  108. Moutier R. New mutations causing sterility restricted to the male in rats and mice. In: Antikatzides T, Erichsen S, Spiegel A. (eds) The laboratory animal in the study of reproduction. Gustuv Fischer, Stuttgart, pp 115–117, 1976.Google Scholar
  109. Nagafuchi S, Namiki M, Nakahori Y, Kondoh N, Okuyama A, Naagome Y. A minute deletion of Y-chromosome in men with azoospermia. J Urol 1993;150:1155–1157.PubMedGoogle Scholar
  110. Najmabadi H, Chai N, Kapali A, et al. Genomic structure of a Y-specific ribonucleic acid binding motif-containing gene: a putative candidate for a subset of male infertility. J Clin Endocrinol Metab 1996;81:2159–2164.PubMedCrossRefGoogle Scholar
  111. Najmabadi H, Huang V, Yen P, et al. Substantial prevalence of microdeletions of the Y-chromosome in infertile men with idiopathic azoospermia detected using a sequence-tagged site based mapping strategy. J Clin Endocrinol Metab 1996; 81:1347–1352.PubMedCrossRefGoogle Scholar
  112. Ohta M, Mitomi T, Kimura M, et al. Anomalies in transgenic mice carrying the human interleukin-2 gene. Tokai J Exp Clin Med 1990; 15:307.PubMedGoogle Scholar
  113. Page DC, Brown LG, de la Chapelle A: Exchange of terminal portions of X and Y chromosomal short arms in human XX males. Nature 1987; 328:437–439.PubMedCrossRefGoogle Scholar
  114. Page DC, de la Chapelle A, Weissenbach J: Chromosome Y specific DNA in related human XX males. Nature 1985; 315:224–226.PubMedCrossRefGoogle Scholar
  115. Paulsen CA, Gordon DL, Carpenter RW, et al. Klinefelter’s syndrome and its variants: a hormonal and chromosomal study. Rec Prog Horm Res 1968;24:321–368.PubMedGoogle Scholar
  116. Pearse RV 2nd, Drollet DW, Kalla KA, et al. Reduced fertility in mice deficient for the POU protein Sperm-1. Proc Natl Acad Sci USA 1997; 94: 7555–7560.PubMedCrossRefGoogle Scholar
  117. Pellas TC, Ramachandran B, Duncan M, et al. Germ cell deficienct (gcd), an insertional mutation manifested as infertility in transgenic mice. Proc natl Acad Sci USA 1991;88:8787–92.PubMedCrossRefGoogle Scholar
  118. Perez-Palacios G, Medina M, Ullaro-Aguirre A, et al. Gonadotropin dynamics in XX males. J Clin Endocinol Metab 1981;53:254–7.CrossRefGoogle Scholar
  119. Phillip M, Arbelle JE, Segev Y, Parvari R. Male hypogonadism due to a mutation in the gene for the beta-subunit of FSH. N Engl J Med 1998;338:1729–32.PubMedCrossRefGoogle Scholar
  120. Pilder SH, Olds-Clarke P, Phillips DM, Silver LM. Hybrid sterility-6: a mouse t complex locus controlling serm flagellar assembly and movement. Dev Biol 1993;159:631–7.PubMedCrossRefGoogle Scholar
  121. Pilder SH, Olds-Clarke P, Phillips DM, Silver LM. Hybrid sterility-6: a mouse t complex locus controlling sperm flagellar assembly and movement. Dev Biol 1993;159:631–7.PubMedCrossRefGoogle Scholar
  122. Quack B, Speed RM, Luciani JM, Noel B, Guichaoua M and Chandley AC. Meiotic analysis of two human reciprocal X-autosome translocations. Cytogenet. Cell Genet. 1988; 48: 43–47.PubMedGoogle Scholar
  123. Raivio T, Huhtaniemi I, Anttila R, Siimes MA, Hagenas L, Nilsson C, Pattersson K, Dunkel L. The role of luteininzing hormone beta gene polymorphism in the onset and progression of puberty in healthy boys. J Clin Endocrinol Metab 1996;81:3278–82.PubMedCrossRefGoogle Scholar
  124. Reijo R, Alagappan RK, Patrizio P, Page DC. Severe oligospermia resulting from deletions of the Azoospermia Factor gene on the Y chromosome. Lancet 1996;347:1290–1293.PubMedCrossRefGoogle Scholar
  125. Reijo R, Lee T-Y, Salo P, et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA binding protein gene. Nature Genetics 1995;10:383–392.PubMedCrossRefGoogle Scholar
  126. Reijo R, Seligman J, Dinlus MB, et al. Mouse autosomal homolog of DAZ, a candidate male sterility gene in humans, is expressed in male germ cells before and after puberty. Genomics 1996;35:346–352.PubMedCrossRefGoogle Scholar
  127. Rieck GW. The XXY syndrome in cattle (bovine hypogonadism). Suppl. 1970; 1:138–145. Giesener Beitr. Erbpath Zuchthyg.Google Scholar
  128. Rimoin DL, Schimke RN. The Gonads, In Rimoin DL, Schimke RN (eds) Genetic Disorders of the Endocrine Glands. St. Louis, Mosby, 258–356, 1971.Google Scholar
  129. Roest HP, van Klaveren J, de Wit J, et al. Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification. Cell. 1996; 86: 799–810.PubMedCrossRefGoogle Scholar
  130. Ross AJ, Waxmire KG, Moss JE, et al. Testicular degeneration in Bclw-deficient mice. Nat Genet. 1998;389:73–77.Google Scholar
  131. Ruggiu M Speed R, Taggart M, et al. The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis. Nature 1997;389:73–77.PubMedCrossRefGoogle Scholar
  132. Russell LB. X-autosome translocations in the mouse: their characterization and use as tools to investigate gene inactivation and gene action. In: Sandberg AA (ed) Cytogenetics of the mammalian X chromosome, part A. Basic mechanisms of X chromosome behaviour. Alan R Liss, New York, 205–250, 1983.Google Scholar
  133. Russell LD, Hikim AP, Overbeek PA, et al. Testis structure in the sys (symplastic spermatids) mouse. Am J Anat 1991;192:169–175.PubMedCrossRefGoogle Scholar
  134. Santen RJ, de Kretser DM, Paulsen CA, Vohees J. Gonadotropins and testosterone in the XYY syndrome. Lancet 1970;2:371–75.PubMedCrossRefGoogle Scholar
  135. Saxena R, Brown LG, Hawkins T, et al. The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned. Nature Genetics 1996;14:292–299.PubMedCrossRefGoogle Scholar
  136. Schiavi RC, Owen D, Fogel M, White D, Szechter R. Pituitary-gonadal function in XYY and XXY men identified in a population survey. Clin Endocrinol (Oxf) 1978;9:233–236.Google Scholar
  137. Searle AG. Nature and consequences of induced chromosome damage in mammals. Genetics 1974; 78: 173–186.PubMedGoogle Scholar
  138. Sharland M, Patton MA, Burch M, et al. A clinical study of Noonan syndrome. Arch Dis Child 1992; 67:178–183.PubMedCrossRefGoogle Scholar
  139. Shellenbarger DL, Cross DP. A new class of male-sterile mutations with combined temperature-sensitive lethal effects in Drosophila melanogaster. Genetics 1977;86:s358.Google Scholar
  140. Simoni M, Gromoll J, Hoppner W, Nieschlag E. Molecular pathophysiology of the pituitary-gonadal axis. Adv Exp Med Biol 1997;424:89–97.PubMedGoogle Scholar
  141. Skakkebaek NE, Giwercman A, and de Kretser DM. Pathogenesis and management of male infertility. Lancet 1994; 343:1473–1479.PubMedCrossRefGoogle Scholar
  142. Sonnenberg-Riethmacher E, Walter B, et al. The C-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis. Genes Dev. 1996; 10: 1184–1193.PubMedGoogle Scholar
  143. Sotomayor RE, and Handel MA. Failure of acrosome assembly in a male sterile mouse mutant. Biol Reprod 1986; 34: 171–182.PubMedCrossRefGoogle Scholar
  144. Stern C. Untersuchungen uber Aberrationen des Y-Chromosoms von Drosophila melanogaster. Z Indukt Abstammungs-Vererbungsl 1929;51:253–353.CrossRefGoogle Scholar
  145. Supp DM, Witte DP, Branford WW, et al. Sp4, a member of the Sp-1 family of zinc finger transcription factors, is required for normal male reproductive behavior. Dev Biol. 1996; 176:284–299.PubMedCrossRefGoogle Scholar
  146. Sutcliffe MJ, Burgoyne PS. Analysis of the testes of H-Y negative XOSxrb mice suggests that the spermatogenesis gene (Spy) acts during the differentiation of the A spermatogonia. Development 1989; 107:373–80.PubMedGoogle Scholar
  147. Swersie S, Hueckel J, Hudson B, Paulsen CA. Endocrine, histologic, and genetic features of the hypogonadism in patients with Down’s syndrome. 53rd Annual Meeting of the Endocrine Society, San Francisco, Abstract 440, 1971.Google Scholar
  148. Takeda R, Ueda M. Pituitary-gonadal function in male patients with myotonic dystrophy-serum LH, FSH, and testosterone levels and histologic damage to the testis. Acta Endocrinol 1977;84:382–9.PubMedGoogle Scholar
  149. Themmen AP, Martens JW, Brunner HG. Gonadotropin receptor mutations. J Endocrinol 1997;153:179–183.PubMedCrossRefGoogle Scholar
  150. Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonflourescent portion of the human Y-chromosome long arm. Hum Genet 1976;34:119–124PubMedCrossRefGoogle Scholar
  151. Tomkiel J. Developmental genetic analysis and molecular cloning of the abnormal oocyte gene of Drosohila melanogaster. Genetics 1995;140:615–627.PubMedGoogle Scholar
  152. Toscani A, Mettus RV, Coupland R, et al. Arrest of spermatogenesis and defective breast development in mice lacking A-myb. Nature 1997;386:713–717.PubMedCrossRefGoogle Scholar
  153. Tsigos C, Latronico C, Chrousos GP. Luteinizing hormone resistance syndromes. Ann N Y Acad Sci 1997;816:263–73.PubMedCrossRefGoogle Scholar
  154. Vergnaud E, Page DC, Simmler MC, et al. Deletion map of the human Y-chromosome based on DNA hybridization. Am J Hum Genet 1986;39:109–124.Google Scholar
  155. Vogt P, and Hennig W. Molecular structure of the lampbrush loop nooses of the Y chromosome of Drosophila hydei. II. DNA sequences with homologies to multiple genomic locations are a major constituent of the loop. Chromosoma (Berl) 1986;94: 459–467.CrossRefGoogle Scholar
  156. Vogt P, Chandley AC, Hargreave TV, Keil R, Ma K, Sharkey A. Microdeletions in interval 6 of the Y-chromosome of male with idiopathic sterility point to disruption of AZF, a human spermatogenesis gene. Hum Genet 1992; 89:491–496.PubMedCrossRefGoogle Scholar
  157. Vollrath D, Foote S, Hilton A, et al. The human Y chromosome: a 43 interval map based on naturally occurring deletions. Science 1992;258;52–59.PubMedCrossRefGoogle Scholar
  158. Waldstreicher J, Seminara SB, Jameson JL, et al. The genetic and clinical heterogeneity of GnRH deficiency in the human. J Clin Endocrinol Metab 1996;81:4388–95.PubMedCrossRefGoogle Scholar
  159. Weiss J, Crowley WF, Jameson JL. Normal structure of the GnRH gene in patients with GnRH deficiency. J Clin Endocrinol Metab 1989;69:299–303.PubMedGoogle Scholar
  160. Whitney MA, Royle G, Low MJ, et al. Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene. Blood 1996;88:49–58.PubMedGoogle Scholar
  161. Xu Y, Ashley T, Brainerd EE, et al. Targeted disruption of ATM leads to growth retardation chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev 1996; 10:2411–2422.PubMedGoogle Scholar
  162. Yokoyama J, Copeland NG, Jenkins NA, et al. Reversal of left right asymmetry: a situs inversus mutation. Science 1993;260:679–684.PubMedCrossRefGoogle Scholar
  163. Zhao GQ, Deng K, Labosky PA, et al. The gene encoding bone mophogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse. Genes Dev. (1996); 10: 1657–1669.PubMedGoogle Scholar
  164. Zhao GQ, Liaw L, Hogan BL. Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of the epididymis. Development 1998; 125:1103–1112.PubMedGoogle Scholar
  165. Zsebo KM, Williams DA, Geissler EN, et al. Stem cell factor is encoded in the SI locus in the mouse and is the ligand for the C-kit tyrosine kinase receptor. Cell 1990;63:213–222.PubMedCrossRefGoogle Scholar
  166. Zuffardi O and Tiepolo L. Frequencies and types of chromosome abnormalities associated with human male infertility. In Genetic Control of Gametic Production and function (eds) P.G. Crosignani and B.L. Rubin. Academic Press, p261–273, 1982.Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • S. Bhasin
    • 1
  • W. E. Taylor
    • 1
  • C. Mallidis
    • 1
  • B. Salehian
    • 1
  • I. Sinha
    • 1
  • M. Limbo
    • 1
  • K. Ma
    • 1
  1. 1.Charles R. Drew University of Medicine and ScienceLos Angeles

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