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Review

Y-Chromosome Microdeletions: A Review of Prevalence, Screening, and Clinical Considerations

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Pages 51-59 | Published online: 12 Feb 2021

References

  • World Health Organization, editor. WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. World Health Organization; 2010.
  • Kumar N, Singh A. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci. 2015;8(4):191. doi:10.4103/0974-1208.170370
  • Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics*‡. Hum Reprod Update. 2010;16(3):231–245. doi:10.1093/humupd/dmp048
  • Hopps CV, Schlegel PN, Goldstein M. 49 - A practical approach to male infertility. In: Legato MJ, editor. Principles of Gender-Specific Medicine. Academic Press; 2004:538–549. doi:10.1016/B978-012440905-7/50318-2.
  • Cocuzza M, Alvarenga C, Pagani R. The epidemiology and etiology of azoospermia. Clinics (Sao Paulo). 2013;68(Suppl 1):15–26. doi:10.6061/clinics/2013(Sup01)03
  • Chiba K, Enatsu N, Fujisawa M. Management of non‐obstructive azoospermia. Reprod Med Biol. 2016;15(3):165–173. doi:10.1007/s12522-016-0234-z
  • Kim SY, Lee BY, Oh AR, Park SY, Lee HS, Seo JT. Clinical, hormonal, and genetic evaluation of idiopathic nonobstructive azoospermia and klinefelter syndrome patients. CGR. 2017;153(4):190–197. doi:10.1159/000487039
  • Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003;423(6942):825–837. doi:10.1038/nature01722
  • Li G, Davis BW, Raudsepp T, et al. Comparative analysis of mammalian Y chromosomes illuminates ancestral structure and lineage-specific evolution. Genome Res. 2013;23(9):1486–1495. doi:10.1101/gr.154286.112
  • Krausz C, Casamonti E. Spermatogenic failure and the Y chromosome. Hum Genet. 2017;136(5):637–655. doi:10.1007/s00439-017-1793-8
  • Janečka JE, Davis BW, Ghosh S, et al. Horse Y chromosome assembly displays unique evolutionary features and putative stallion fertility genes. Nat Commun. 2018;9(1):2945. doi:10.1038/s41467-018-05290-6
  • Oetjens MT, Shen F, Emery SB, Zou Z, Kidd JM. Y-chromosome structural diversity in the bonobo and chimpanzee lineages. Genome Biol Evol. 2016;8(7):2231–2240. doi:10.1093/gbe/evw150
  • Lahn BT, Pearson NM, Jegalian K. The human Y chromosome, in the light of evolution. Nat Rev Genet. 2001;2(3):207–216. doi:10.1038/35056058
  • Das PP, Krishnan G, Doley J, et al. Identification and expression profiling of MSY genes of yak for bull fertility. J Genet. 2019;98(2). doi:10.1007/s12041-019-1091-4.
  • Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human y chromosome long arm. Hum Genet. 1976;34(2):119–124. doi:10.1007/BF00278879
  • Vog PH, Edelmann A, Kirsch S, et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996;5(7):933–943. doi:10.1093/hmg/5.7.933
  • Krausz C, Hoefsloot L, Simoni M, Tüttelmann 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(1):5–19. doi:10.1111/j.2047-2927.2013.00173.x
  • Navarro-Costa P, Pereira L, Alves C, et al. Characterizing partial AZFc deletions of the Y chromosome with amplicon-specific sequence markers. BMC Genomics. 2007;8:342. doi:10.1186/1471-2164-8-342
  • Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015;103(3):e18–e25. doi:10.1016/j.fertnstert.2014.12.103
  • Krausz C, Forti G, McElreavey K. The Y chromosome and male fertility and infertility1. Int J Androl. 2003;26(2):70–75. doi:10.1046/j.1365-2605.2003.00402.x
  • Kohn TP, Kohn JR, Owen RC, Coward RM. The prevalence of Y-chromosome microdeletions in oligozoospermic men: a systematic review and meta-analysis of European and North American studies. Eur Urol. 2019;76(5):626–636. doi:10.1016/j.eururo.2019.07.033
  • Jungwirth A, Diemer T, Feng Z, Krausz C, Minhas S, Tournaye H. EAU Guidelines on Male Infertility. EAU Guidelines Office; 2018.
  • Simoni M, Tüttelmann F, Gromoll J, Nieschlag E. Clinical consequences of microdeletions of the Y chromosome: the extended Münster experience. Reprod Biomed Online. 2008;16(2):289–303. doi:10.1016/S1472-6483(10)60588-3
  • Iijima M, Shigehara K, Igarashi H, et al. Y chromosome microdeletion screening using a new molecular diagnostic method in 1030 Japanese males with infertility. Asian J Androl. 2019;22(4):368–371. doi:10.4103/aja.aja_97_19
  • Park SH, Lee HS, Choe JH, Lee JS, Seo JT. Success rate of microsurgical multiple testicular sperm extraction and sperm presence in the ejaculate in Korean Men with Y chromosome microdeletions. Korean J Urol. 2013;54(8):536–540. doi:10.4111/kju.2013.54.8.536
  • Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. Fertil Steril. 2015;104(5):1099–1103.e3. doi:10.1016/j.fertnstert.2015.07.1136
  • Silber SJ. The Y chromosome in the era of intracytoplasmic sperm injection: a personal review. Fertil Steril. 2011;95(8):2439–2448.e5. doi:10.1016/j.fertnstert.2011.05.070
  • Brandell RA, Mielnik A, Liotta D, et al. AZFb deletions predict the absence of spermatozoa with testicular sperm extraction: preliminary report of a prognostic genetic test. Hum Reprod. 1998;13(10):2812–2815. doi:10.1093/humrep/13.10.2812
  • Stouffs K, Vloeberghs V, Gheldof A, Tournaye H, Seneca S. Are AZFb deletions always incompatible with sperm production? Andrology. 2017;5(4):691–694. doi:10.1111/andr.12350
  • Fernandes S, Huellen K, Goncalves J, et al. High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia. Mol Hum Reprod. 2002;8(3):286–298. doi:10.1093/molehr/8.3.286
  • Krausz C, Chianese C, Giachini C, Guarducci E, Laface I, Forti G. The Y chromosome-linked copy number variations and male fertility. J Endocrinol Invest. 2011;34(5):376–382. doi:10.1007/BF03347463
  • 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. Nat Genet. 1996;14(3):292–299. doi:10.1038/ng1196-292
  • Seboun E, Barbaux S, Bourgeron T, et al. Gene sequence, localization, and evolutionary conservation of DAZLA, a candidate male sterility gene. Genomics. 1997;41(2):227–235. doi:10.1006/geno.1997.4635
  • Yen PH, Chai NN, Salido EC. The human autosomal gene DAZLA: testis specificity and a candidate for male infertility. Hum Mol Genet. 1996;5(12):2013–2017. doi:10.1093/hmg/5.12.2013
  • Silber SJ, Repping S. Transmission of male infertility to future generations: lessons from the Y chromosome. Hum Reprod Update. 2002;8(3):217–229. doi:10.1093/humupd/8.3.217
  • Cariati F, D’Argenio V, Tomaiuolo R. The evolving role of genetic tests in reproductive medicine. J Transl Med. 2019;17. doi:10.1186/s12967-019-2019-8.
  • Peterlin B, Kunej T, Sinkovec J, Gligorievska N, Zorn B. Screening for Y chromosome microdeletions in 226 Slovenian subfertile men. Hum Reprod. 2002;17(1):17–24. doi:10.1093/humrep/17.1.17
  • Liu X, Li Z, Su Z, et al. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs). Sci Rep. 2016;6. doi:10.1038/srep21831
  • Poznik GD, Henn BM, Yee M-C, et al. Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females. Science. 2013;341(6145):562–565. doi:10.1126/science.1237619
  • Krausz C, Degl’Innocenti S, Nuti F, et al. Natural transmission of USP9Y gene mutations: a new perspective on the role of AZFa genes in male fertility. Hum Mol Genet. 2006;15(18):2673–2681. doi:10.1093/hmg/ddl198
  • Kleiman SE, Yogev L, Lehavi O, et al. The likelihood of finding mature sperm cells in men with AZFb or AZFb-c deletions: six new cases and a review of the literature (1994–2010). Fertil Steril. 2011;95(6):2005–2012.e4. doi:10.1016/j.fertnstert.2011.01.162
  • Repping S, Skaletsky H, Lange J, 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(4):906–922. doi:10.1086/342928
  • Jaruzelska J, Korcz A, Wojda A, et al. Mosaicism for 45,X cell line may accentuate the severity of spermatogenic defects in men with AZFc deletion. J Med Genet. 2001;38(11):798–802. doi:10.1136/jmg.38.11.798
  • Suganthi R, Vijesh VV, Vandana N, Fathima Ali Benazir J. Y chromosomal microdeletion screening in the workup of male infertility and its current status in India. Int J Fertil Steril. 2014;7(4):253–266.
  • Dada R, Kumar R, Shamsi MB, et al. Higher frequency of Yq microdeletions in sperm DNA as compared to DNA isolated from blood. Asian J Androl. 2007;9(5):720–722. doi:10.1111/j.1745-7262.2007.00274.x
  • Sakthivel PJ, Swaminathan M. Y chromosome microdeletions in sperm DNA of infertile patients from Tamil Nadu, south India. Indian J Urol. 2008;24(4):480–485. doi:10.4103/0970-1591.44252
  • Le Bourhis C, Siffroi JP, McElreavey K, Dadoune JP. Y chromosome microdeletions and germinal mosaicism in infertile males. Mol Hum Reprod. 2000;6(8):688–693. doi:10.1093/molehr/6.8.688
  • Levine H, Jørgensen N, Martino-Andrade A, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017;23(6):646–659. doi:10.1093/humupd/dmx022
  • Sengupta P, Dutta S, Krajewska-Kulak E. The disappearing sperms: analysis of reports published between 1980 and 2015. Am J Mens Health. 2017;11(4):1279–1304. doi:10.1177/1557988316643383
  • Johnson M, Raheem A, De Luca F, et al. An analysis of the frequency of Y-chromosome microdeletions and the determination of a threshold sperm concentration for genetic testing in infertile men. BJU Int. 2019;123(2):367–372. doi:10.1111/bju.14521
  • Liu JL, Peña V, Fletcher SA, Kohn TP. Genetic testing in male infertility – reassessing screening thresholds. Curr Opin Urol. 2020;30(3):317–323. doi:10.1097/MOU.0000000000000764
  • Wu AK, Odisho AY, Washington SL, Katz PP, Smith JF. Out-of-pocket fertility patient expense: data from a multicenter prospective infertility Cohort. J Urol. 2014;191(2):427–432. doi:10.1016/j.juro.2013.08.083
  • Ortac M, Ergul R, Gurcan M, et al. Indication for Y chromosome microdeletion analysis in infertile men: is a new sperm concentration threshold needed? Urology. 2020;146:113–117. doi:10.1016/j.urology.2020.09.032
  • Lin Y-W, Hsu -LC-L, Kuo P-L, et al. Partial duplication at AZFc on the Y chromosome is a risk factor for impaired spermatogenesis in Han Chinese in Taiwan. Hum Mutat. 2007;28(5):486–494. doi:10.1002/humu.20473
  • Zhou R, Cheng J, Ma D, et al. Identifying novel copy number variants in azoospermia factor regions and evaluating their effects on spermatogenic impairment. Front Genet. 2019;10:427. doi:10.3389/fgene.2019.00427
  • Repping S, Skaletsky H, Brown L, et al. Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection. Nat Genet. 2003;35(3):247–251. doi:10.1038/ng1250
  • de Llanos M, Ballescà JL, Gázquez C, Margarit E, Oliva R. High frequency of gr/gr chromosome Y deletions in consecutive oligospermic ICSI candidates. Hum Reprod. 2005;20(1):216–220. doi:10.1093/humrep/deh582
  • Ferlin A, Tessari A, Ganz F, et al. Association of partial AZFc region deletions with spermatogenic impairment and male infertility. J Med Genet. 2005;42(3):209–213. doi:10.1136/jmg.2004.025833
  • Giachini C, Laface I, Guarducci E, Balercia G, Forti G, Krausz C. Partial AZFc deletions and duplications: clinical correlates in the Italian population. Hum Genet. 2008;124(4):399–410. doi:10.1007/s00439-008-0561-1
  • Rozen SG, Marszalek JD, Irenze K, et al. AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes. Am J Hum Genet. 2012;91(5):890–896. doi:10.1016/j.ajhg.2012.09.003
  • Levkova M, Chervenkov T, Angelova L. The association of gr/gr deletion in the Y chromosome and impaired spermatogenesis in Bulgarian males: a pilot study. Middle East Fertil Soc J. 2020;25(1):10. doi:10.1186/s43043-020-00020-9
  • Hucklenbroich K, Gromoll J, Heinrich M, Hohoff C, Nieschlag E, Simoni M. Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis. Hum Reprod. 2005;20(1):191–197. doi:10.1093/humrep/deh558
  • Xie S, Zhang Y, Yang Y. Is the primary AZFc duplication a potential risk for male infertility?: A systematic review and meta-analysis. Andrology. 2020;8(5):996–1004. doi:10.1111/andr.12800
  • Zhang F, Lu C, Li Z, et al. Partial deletions are associated with an increased risk of complete deletion in AZFc: a new insight into the role of partial AZFc deletions in male infertility. J Med Genet. 2007;44(7):437–444. doi:10.1136/jmg.2007.049056
  • Moreno-Mendoza D, Casamonti E, Paoli D, et al. gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study. Eur J Hum Genet. 2019;27(10):1578–1588. doi:10.1038/s41431-019-0420-7