Chromosomal Translocations and Inversion in Male Infertility

  • Kareim Khalafalla
  • Pallav Sengupta
  • Mohamed Arafa
  • Ahmad Majzoub
  • Haitham Elbardisi


Chromosomal abnormalities are major contributors of idiopathic male infertility. Anomalies or mutations of the chromosomal DNA lead to different forms of chromosomal abnormalities. An array of functional gene expressions determines normal testicular development and robust spermatogenesis. In case of any anomalies in these genes, testicular dysgenesis as well as spermatogenic arrest may occur leading to a comprised state of male fertility. The present chapter will review two of the most sophisticated structural chromosomal abnormalities, translocation and inversion. Chromosomal translocation refers to the transfer of chromosomal part to another chromosome, while genetic inversion takes place when a chromosomal part breaks off, rotates 180 degrees, and reattaches to the same chromosome. Moreover, the chapter aims to present the underlying mechanisms by which chromosomal translocations and inversions pave the way to male infertility, clinical presentations of related conditions, and management approach in cases of chromosomal abnormalities-induced male infertility.


Chromosomal aberrations Inversions Male infertility Translocations 


  1. 1.
    Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl. 2012;14(1):32.PubMedCrossRefGoogle Scholar
  2. 2.
    Naasse Y, Charoute H, El Houate B, Elbekkay C, Razoki L, Malki A, Barakat A, Rouba H. Chromosomal abnormalities and Y chromosome microdeletions in infertile men from Morocco. BMC Urol. 2015;15(1):95.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Sha J, Group SS, Zhou Z, Group SS, Li J, Group SS, Yin L, Group SS, Yang H, Group SS. Identification of testis development and spermatogenesis-related genes in human and mouse testes using cDNA arrays. Mol Hum Reprod. 2002;8(6):511–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Bezold G, Lange M, Peter RU. Homozygous methylenetetrahydrofolate reductase C677T mutation and male infertility. N Engl J Med. 2001;344(15):1172–3.PubMedCrossRefGoogle Scholar
  5. 5.
    Ramanujam L, Liao W-X, Roy A, Ng S. Association of molecular variants of luteinizing hormone with male infertility. Hum Reprod. 2000;15(4):925–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Van der Ven K, Fimmers R, Engels G, Van der Ven H, Krebs D. Evidence for major histocompatibility complex-mediated effects on spermatogenesis in humans. Hum Reprod. 2000;15(1):189–96.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Fritsche E, Schuppe HC, Döhr O, Ruzicka T, Gleichmann E, Abel J. Increased frequencies of cytochrome P4501A1 polymorphisms in infertile men. Andrologia. 1998;30(3):125–8.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Chandley AC, Edmond P, Christie S, Gowans L, Fletcher J, Frackiewicz A, Newton M. 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. 1975;39(2):231–54.PubMedCrossRefGoogle Scholar
  9. 9.
    Gardner RM, Sutherland GR, Shaffer LG. Chromosome abnormalities and genetic counseling. New York/Oxford: OUP; 2011.CrossRefGoogle Scholar
  10. 10.
    Aplan PD. Causes of oncogenic chromosomal translocation. Trends Genet. 2006;22(1):46–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Hsu LY. Phenotype/karyotype correlations of Y chromosome aneuploidy with emphasis on structural aberrations in postnatally diagnosed cases. Am J Med Genet. 1994;53(2):108–40.PubMedCrossRefGoogle Scholar
  12. 12.
    Gödde-Salz E, Behnke H. Aniridia, mental retardation and an unbalanced reciprocal translocation of chromosomes 8 and 11 with an interstitial deletion of 11p. Eur J Pediatr. 1981;136(1):93–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhang K, Dong R, Huang Y, Yang Y, Wang Y, Zhang H, Zhang Y, Liu Y, Gai Z. Clinical and molecular cytogenetic analysis of a family with mental retardation caused by an unbalanced translocation involving chromosomes 3 and 22. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, J Med Genet. 2017;34(1):30–4.Google Scholar
  14. 14.
    Wilch ES, Morton CC. Historical and clinical perspectives on chromosomal translocations. Adv Exp Med Biol, Springer. 2018;1044:1–14.CrossRefGoogle Scholar
  15. 15.
    Sha Y-W, Mei L-B, Ji Z-Y, Ding L, Ge Y, Wu Q, Kong H, Su Z-Y, Li P. Two cases of complex balanced autosomal translocations associated with severe oligozoospermia. Gene. 2018;663:126–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Aftab A, Varma TR, Kar B. A rare case of de novo balanced reciprocal Y: 1 chromosomal translocation in patient presenting with azoospermia. Andrologia. 2019;51(4):e13246.PubMedCrossRefGoogle Scholar
  17. 17.
    Mikelsaar R, Pauklin M, Lissitsina J, Punab M. Reciprocal translocation t (7; 16)(q21. 2; p13. 3) in an infertile man. Fertil Steril. 2006;86(3):719. e9–e11.CrossRefGoogle Scholar
  18. 18.
    Aydos SE, Tükün A. Infertility in a man with oligoasthenoteratozoospermia associated with nonrobertsonian translocation t (9; 15)(p10; q10). Fertil Steril. 2006;86(4):1001.e7–.e9.CrossRefGoogle Scholar
  19. 19.
    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 Genome Res. 1985;39(1):19–29.CrossRefGoogle Scholar
  20. 20.
    Sullivan GJ, Bridger JM, Cuthbert AP, Newbold RF, Bickmore WA, McStay B. Human acrocentric chromosomes with transcriptionally silent nucleolar organizer regions associate with nucleoli. EMBO J. 2001;20(11):2867–77.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Biricik A, Guney I, Berkil H, Benkhalifa M, Kahraman S. A male (15; 15) Robertsonian translocation case with 11 previous consecutive recurrent spontaneous abortions. Marmara Med J. 2004;17(1):35–8.Google Scholar
  22. 22.
    Fryns J, Kleczkowska A, Kubien E. Structural chromosomal rearrangements in couples with repeated miscarriages. Experience in Louvain. J de genetique humaine. 1988;36(1-2):59–61.Google Scholar
  23. 23.
    Kaiser P. Pericentric inversions. Hum Genet. 1984;68(1):1–47.PubMedCrossRefGoogle Scholar
  24. 24.
    Madan K. Paracentric inversions: a review. Hum Genet. 1995;96(5):503–15.PubMedCrossRefGoogle Scholar
  25. 25.
    Muthuvel A, Ravindran M, Chander A, Subbian C. Pericentric inversion of chromosome 9 causing infertility and subsequent successful in vitro fertilization. Niger Med J. 2016;57(2):142.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Wiland E, Wojda A, Kamieniczna M, Szczygieł M, Kurpisz M. Infertility status of male individuals with abnormal spermiogram evaluated by cytogenetic analysis and in vitro sperm penetration assay. Med Sci Monit. 2002;8(5):CR394–400.PubMedGoogle Scholar
  27. 27.
    Therman E, Susman B, Denniston C. The nonrandom participation of human acrocentric chromosomes in Robertsonian translocations. Ann Hum Genet. 1989;53(1):49–65.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Nielsen J, Wohlert M. Chromosome abnormalities found among 34910 newborn children: results from a 13-year incidence study in Århus, Denmark. Hum Genet. 1991;87(1):81–3.PubMedCrossRefGoogle Scholar
  29. 29.
    Mak V, Jarvi KA. The genetics of male infertility. J Urol. 1996;156(4):1245–57.PubMedCrossRefGoogle Scholar
  30. 30.
    Gunel M, Cavkaytar S, Ceylaner G, Batioglu S. Azoospermia and cryptorchidism in a male with a de novo reciprocal t (Y; 16) translocation. Genet Couns. 2008;19(3):277.PubMedGoogle Scholar
  31. 31.
    Mau-Holzmann U. Somatic chromosomal abnormalities in infertile men and women. Cytogenet Genome Res. 2005;111(3-4):317–36.CrossRefGoogle Scholar
  32. 32.
    Demirhan O, Pazarbaşı A, Suleymanova-Karahan D, Tanriverdi N, Kılınç Y. Correlation of clinical phenotype with a pericentric inversion of chromosome 9 and genetic counseling. Saudi Med J. 2008;29:946–51.PubMedGoogle Scholar
  33. 33.
    Serra A, Brahe C, Millington-Ward A, Neri G, Tedeschi B, Tassone F, Bova R. Pericentric inversion of chromosome 9: prevalence in 300 down syndrome families and molecular studies of nondisjunction. Am J Med Genet. 1990;37(S7):162–8.CrossRefGoogle Scholar
  34. 34.
    Wang D, Chen R, Kong S, Pan QY, Zheng YH, Qiu WJ, Fan Y, Sun XF. Cytogenic and molecular studies of male infertility in cases of Y chromosome balanced reciprocal translocation. Mol Med Rep. 2017;16(2):2051–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Ferlin A, Dipresa S, Delbarba A, Maffezzoni F, Porcelli T, Cappelli C, Foresta C. Contemporary genetics-based diagnostics of male infertility. Expert Rev Mol Diagn. 2019;19(7):623–33.PubMedCrossRefGoogle Scholar
  36. 36.
    Steger K, Failing K, Klonisch T, Behre HM, Manning M, Weidner W, Hertle L, Bergmann M, Kliesch S. Round spermatids from infertile men exhibit decreased protamine-1 and-2 mRNA. Hum Reprod. 2001;16(4):709–16.PubMedCrossRefGoogle Scholar
  37. 37.
    Domenjoud L, Kremling H, Burfeind P, Maier WM, Engel W. On the expression of protamine genes in the testis of man and other mammals. Andrologia. 1991;23(5):333–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Forejt J, editor. XY involvement in male sterility caused by autosome translocations a hyphothesis. Serono cli Colloq Reprod; 1982.Google Scholar
  39. 39.
    Chandley A, Speed R, McBeath S, Hargreave T. A human 9; 20 reciprocal translocation associated with male infertility analyzed at prophase and metaphase I of meiosis. Cytogenet Genome Res. 1986;41(3):145–53.CrossRefGoogle Scholar
  40. 40.
    Madan K, Hompes P, Schoemaker J, Ford C. X-autosome translocation with a breakpoint in Xq22 in a fertile woman and her 47, XXX infertile daughter. Hum Genet. 1981;59(4):290–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Szvetko A, Martin N, Joy C, Hayward A, Watson B, Cary A, Withers S. Detection of chromosome x; 18 breakpoints and translocation of the xq22. 3; 18q23 regions resulting in variable fertility phenotypes. Case Rep Genet. 2012;2012:681747.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Jiang Y-T, Zhang H-G, Wang R-X, Yu Y, Zhang Z-H, Liu R-Z. Novel Y chromosome breakpoint in an infertile male with a de novo translocation t (Y; 16): a case report. J Assist Reprod Genet. 2012;29(12):1427–30.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Stahl A, Hartung M, Vagner-Capodano A, Fouet C. Chromosomal constitution of nucleolus-associated chromatin in man. Hum Genet. 1976;35(1):27–34.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Guichaoua M, Gabriel-Robez O, Ratomponirina C, Delafontaine D, Le BM, Taillemite J, Rumpler Y, Luciani J. Meiotic behaviour of familial pericentric inversions of chromosomes 1 and 9. Annales de genetique. 1986;29:207–14.PubMedGoogle Scholar
  45. 45.
    Chandley A, McBeath S, Speed R, Yorston L, Hargreave T. Pericentric inversion in human chromosome 1 and the risk for male sterility. J Med Genet. 1987;24(6):325–34.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Anton E, Blanco J, Egozcue J, Vidal F. Risk assessment and segregation analysis in a pericentric inversion inv (6)(p23q25) carrier using FISH on decondensed sperm nuclei. Cytogenet Genome Res. 2002;97(3-4):149–54.PubMedCrossRefGoogle Scholar
  47. 47.
    Balasar Ö, Zamani AG, Balasar M, Acar H. Male infertility associated with de novo pericentric inversion of chromosome 1. Turk J Urol. 2017;43(4):560.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Kumar R, Tanwar M, Ammini AC, Kumar R, Gupta NP, Sharma RK, Dada R. Robertsonian translocation and their role in pathogenesis of recurrent in vitro fertilization failure. Med Sci Monit. 2008;14(12):CR617–CR20.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Brezina PR, Ke RW, Kutteh WH. Preimplantation genetic screening: a practical guide. Clin Med Insights Reprod Health. 2013;7:CMRH. S10852.CrossRefGoogle Scholar
  50. 50.
    Liss J, Chromik I, Szczyglińska J, Jagiełło M, Łukaszuk A, Łukaszuk K. Current methods for preimplantation genetic diagnosis. Ginekol Pol. 2016;87(7):522–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Kass LR. The wisdom of repugnance: why we should ban the cloning of humans. Val UL Rev. 1997;32:679.Google Scholar
  52. 52.
    Kass LR. Triumph or tragedy? The moral meaning of genetic technology. Am J Jurisprud. 2000;45(1):1–16.PubMedCrossRefGoogle Scholar
  53. 53.
    Kass L. Life, liberty and the defense of dignity: the challenge for bioethics. New York: Encounter Books; 2002.Google Scholar
  54. 54.
    Chang EM, Han JE, Kwak IP, Lee WS, Yoon TK, Shim SH. Preimplantation genetic diagnosis for couples with a Robertsonian translocation: practical information for genetic counseling. J Assist Reprod Genet. 2012;29(1):67–75.PubMedCrossRefGoogle Scholar
  55. 55.
    Capalbo A, Romanelli V, Cimadomo D, Girardi L, Stoppa M, Dovere L, Dell’Edera D, Ubaldi FM, Rienzi L. Implementing PGD/PGD-A in IVF clinics: considerations for the best laboratory approach and management. J Assist Reprod Genet. 2016;33(10):1279–86.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Chamayou S, Sicali M, Lombardo D, Alecci C, Guglielmino A. The decision on the embryo to transfer after preimplantation genetic diagnosis for X-autosome reciprocal translocation in male carrier. Mol Cytogenet. 2018;11(1):63.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Dul E, van Echten-Arends J, Groen H, Kastrop P, Wissen L, Engelen J, Land J, Coonen E, van Ravenswaaij-Arts C. Can characteristics of reciprocal translocations predict the chance of transferable embryos in PGD cycles? J Clin Med. 2014;3(2):348–58.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Verlinsky Y, Rechitsky S, Sharapova T, Morris R, Taranissi M, Kuliev A. Preimplantation HLA testing. JAMA. 2004;291(17):2079–85.PubMedCrossRefGoogle Scholar
  59. 59.
    Vastag B. Merits of embryo screening debated. JAMA. 2004;291(8):927–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Ogilvie CM, Braude PR, Scriven PN. Preimplantation genetic diagnosis—an overview. J Histochem Cytochem. 2005;53(3):255–60.PubMedCrossRefGoogle Scholar
  61. 61.
    Sills ES, Kim JJ, Witt MA, Palermo GD. Non-obstructive azoospermia and maturation arrest with complex translocation 46, XY t (9; 13; 14)(p22; q21. 2; p13) is consistent with the Luciani-Guo hypothesis of latent aberrant autosomal regions and infertility. Cell Chromosome. 2005;4(1):2.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Baccetti B, Bruni E, Collodel G, Gambera L, Moretti E, Marzella R, Piomboni P. 10, 15 reciprocal translocation in an infertile man: ultrastructural and fluorescence in-situ hybridization sperm study: case report. Hum Reprod. 2003;18(11):2302–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Gu L, Zhang H, Zhu G. Impact of reciprocal translocation t (18; 21) on male infertility and embryo development: lessons from an oocyte-donating ICSI cycle. J Assist Reprod Genet. 2011;28(7):603.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Oakley J, Else P, Asplin P, Taitz L. Balanced translocation, impaired sperm motility, and offspring anomaly. Arch Dis Child. 1976;51(8):638–40.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Arafa MM, Majzoub A, AlSaid SS, El Ansari W, Al Ansari A, Elbardisi Y, Elbardisi HT. Chromosomal abnormalities in infertile men with azoospermia and severe oligozoospermia in Qatar and their association with sperm retrieval intracytoplasmic sperm injection outcomes. Arab J Urol. 2018;16(1):132–9.CrossRefGoogle Scholar
  66. 66.
    Alves C, Carvalho F, Cremades N, Sousa M, Barros A. Unique (Y; 13) translocation in a male with oligozoospermia: cytogenetic and molecular studies. Eur J Hum Genet. 2002;10(8):467.PubMedCrossRefGoogle Scholar
  67. 67.
    Faed M, Lamont M, Baxby K. Cytogenetic and histological studies of testicular biopsies from subfertile men with chromosome anomaly. J Med Genet. 1982;19(1):49–56.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Abeliovich D, Potashnik G, Dar H, Lugasi N, Rave D. Chromosomal rearrangements in three infertile men. Andrologia. 1986;18(2):147–51.PubMedCrossRefGoogle Scholar
  69. 69.
    Gregori-Romero M, López-Ginés C, Gil R, Galán FS, Pellín-Pérez A. 2 new cases of Y-autosome translocation associated with azoospermia. Rev Clin Esp. 1990;187(2):71–3.PubMedGoogle Scholar
  70. 70.
    Giltay J, Tiemessen C, Van Inzen W, Scheres J. One normal child and a chromosomally balanced/normal twin after intracytoplasmic sperm injection in a male with a de-novo t (Y; 16) translocation. Hum Reprod. 1998;13(10):2745–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Siffroi JP, Benzacken B, Angelopoulou R, Le Bourhis C, Berthaut I, Kanafani S, Smahi A, Wolf JP, Dadoune JP. Alternative centromeric inactivation in a pseudodicentric t (Y; 13)(q12; p11. 2) translocation chromosome associated with extreme oligozoospermia. J Med Genet. 2001;38(11):802–6.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Ishikawa T, Kondo Y, Yamaguchi K, Oba T, Sakamoto Y, Takenaka A, Fujisawa M. An unusual reciprocal X-autosome translocation in an infertile azoospermic man. Fertil Steril. 2007;88(3):705. e15-e17.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Kareim Khalafalla
    • 1
  • Pallav Sengupta
    • 2
  • Mohamed Arafa
    • 3
  • Ahmad Majzoub
    • 3
  • Haitham Elbardisi
    • 3
  1. 1.Department of UrologyHamad General HospitalDohaQatar
  2. 2.Department of Physiology, Faculty of Medicine, Bioscience and NursingMAHSA UniversityJenjarom, SelangorMalaysia
  3. 3.Department of UrologyHamad Medical CorporationDohaQatar

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