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Journal of Assisted Reproduction and Genetics

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01-06-2012 | Genetics

Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men

Authors: Li Fu, Da-Ke Xiong, Xian-Ping Ding, Chuang Li, Li-Yuan Zhang, Min Ding, Shuang-Shuang Nie, Qiang Quan

Published in: Journal of Assisted Reproduction and Genetics | Issue 6/2012

Abstract

Purposes

To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men.

Methods

This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reactio(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia.

Results

Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P < 0.01). Also 144 of 1,333(10.80%) patients presented Y chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls.

Conclusions

There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

Akin H, Onay H, Turker E, Ozkinay F. Primary male infertility in Izmir/Turkey: a cytogenetic and molecular study of 187 infertile Turkish patients. J Assist Reprod Genet. 2011;1–5.

Ali M, Hayat M. Screening of ‘Y’ chromosome microdeletions in Iranian infertile males. J Hum Reprod Sci. 2008;1:2–9.CrossRef

Brennan J, Capel B. One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 2004;5(7):509–21.PubMedCrossRef

Carrell D, De Jonge C, Lamb D. The genetics of male infertility: a field of study whose time is now. Syst Biol Reprod Med. 2006;52(4):269–74.CrossRef

Carrell DT. Contributions of spermatozoa to embryogenesis: assays to evaluate their genetic and epigenetic fitness. Reprod Biomed Online. 2008;16(4):474–84.PubMedCrossRef

Chapelle A. The etiology of maleness in XX men. Hum Genet. 1981;58(1):105–16.PubMedCrossRef

De Kretser D. Male infertility. Lancet. 1997;349(9054):787.PubMedCrossRef

De Kretser D, Baker H. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab. 1999;84(10):3443.PubMedCrossRef

El Awady MK, El Shater SF, Ragaa E, Atef K, Shaheen IM, Megiud NA. Molecular study on Y chromosome microdeletions in Egyptian males with idiopathic infertility. Asian J Androl. 2004;6(1):53–8.PubMed

10.

Elghezal H, Hidar S, Braham R, Denguezli W, Ajina M, Saâd A. Chromosome abnormalities in one thousand infertile males with nonobstructive sperm disorders. Fertil Steril. 2006;86(6):1792–5.PubMedCrossRef

11.

Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, Lenzi A, Foresta C. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab. 2007;92(3):762.PubMedCrossRef

12.

Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C. Male infertility: role of genetic background. Reprod BioMed Online. 2007;14(6):734–45.PubMedCrossRef

13.

Foresta C, Garolla A, Bartoloni L, Bettella A, Ferlin A. Genetic abnormalities among severely oligospermic men who are candidates for intracytoplasmic sperm injection. J Clin Endocrinol Metab. 2005;90(1):152.PubMedCrossRef

14.

Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev. 2001;22(2):226–39.PubMedCrossRef

15.

Hofherr SE, Wiktor AE, Kipp BR, Dawson DB, Van Dyke DL. Clinical diagnostic testing for the cytogenetic and molecular causes of male infertility: the Mayo Clinic experience. J Assist Reprod Genet. 2011;1–8.

16.

Jaruzelska J, Korcz A, Wojda A, Jedrzejczak P, Bierla J, Surmacz T, Pawelczyk L, Page DC, Kotecki M. 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.PubMedCrossRef

17.

Lian J, Zhang X, Tian H, Liang N, Wang Y, Liang C, Li X, Sun F. Altered microRNA expression in patients with non-obstructive azoospermia. Reprod Biol Endocrinol. 2009;7:13.PubMedCrossRef

18.

Mahanta R, Gogoi A, Roy S, Bhattacharyya I, Sharma P. Prevalence of Azoospermia Factor (AZF) deletions in idiopathic infertile males in North-East India. Int J Hum Genet. 2011;11(2):99–104.

19.

Margarit E, Soler A, Carrio A, Oliva R, Costa D, Vendrell T, Rosell J, Ballesta F. Molecular, cytogenetic, and clinical characterisation of six XX males including one prenatal diagnosis. J Med Genet. 1998;35(9):727–30.PubMedCrossRef

20.

Martinez-Garza SG, Gallegos-Rivas MC, Vargas-Maciel M, Rubio-Rubio JM, de los Monteros-Rodriguez ME, Gonzalez-Ortega C, Cancino-Villarreal P, de Lara LGV, Gutierrez-Gutierrez AM. Genetic screening in infertile Mexican men: chromosomal abnormalities, Y chromosome deletions, and androgen receptor CAG repeat length. J Androl. 2008;29(6):654.PubMedCrossRef

21.

Organization WH. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999.

22.

Paquis-Flucklinger V, Santucci-Darmanin S, Paul R, Saunieres A, Turc-Carel C, Desnuelle C. Cloning and expression analysis of a meiosis-specific MutS homolog: the HumanMSH4Gene. Genomics. 1997;44(2):188–94.PubMedCrossRef

23.

Patsalis PC, Sismani C, Quintana-Murci L, Taleb-Bekkouche F, Krausz C, McElreavey K. Effects of transmission of Y chromosome AZFc deletions. Lancet. 2002;360(9341):1222–4.PubMedCrossRef

24.

Repping S, Skaletsky H, Lange J, Silber S, Van der Veen F, Oates RD, Page DC, Rozen S. Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure. Am J Hum Genet. 2002;71(4):906–22.PubMedCrossRef

25.

Shaffer LG, Tommerup N. ISCN 2005: an international system for human cytogenetic nomenclature (2005): recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. S Karger Pub. 2005.

26.

Simoni M, Bakker E, Krausz C. EAA/EMQN best practice guidelines for molecular diagnosis of y-chromosomal microdeletions. State of the art 2004. Int J Androl. 2004;27(4):240–9.PubMedCrossRef

27.

Simoni M, Tuttelmann 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.PubMedCrossRef

28.

Sinclair A, Berta P, Palmer M, Hawkins J, Griffiths B. A gene from the human sex-determining region encodes a protein with. Nature. 1990;346(6281):240–4.PubMedCrossRef

29.

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):119–24.PubMedCrossRef

30.

Van Assche E, Bonduelle M, Tournaye H, Joris H, Verheyen G, Devroey P, Van Steirteghem A, Liebaers I. Cytogenetics of infertile men. Hum Reprod. 1996;11 suppl 4:1.PubMedCrossRef

31.

Velasco G, Pendás AM, Fueyo A, Knäuper V, Murphy G, López-Otín C. Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. J Biol Chem. 1999;274(8):4570.PubMedCrossRef

32.

Vog P, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, Köhn F, Schill W, Farah S, Ramos C. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996;5(7):933.CrossRef

33.

Wang RX, Fu C, Yang YP, Han RR, Dong Y, Dai RL, Liu RZ. Male infertility in China: laboratory finding for AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China. J Assist Reprod Genet. 2010;27(7):391–6.PubMedCrossRef

34.

Wong WY, Thomas CMG, Merkus JMWM, Zielhuis GA, Steegers-Theunissen RPM. Male factor subfertility: possible causes and the impact of nutritional factors. Fertil Steril. 2000;73(3):435–42.PubMedCrossRef

35.

Yang Y, Ma M, Xiao C, Li L, Li S, Zhang S. Massive deletion in AZFb/b+ c and azoospermia with sertoli cell only and/or maturation arrest. Int J Androl. 2008;31(6):573–8.PubMedCrossRef

36.

Zhang F, Lu C, Li Z, Xie P, Xia Y, Zhu X, Wu B, Cai X, Wang X, Qian J. 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):437–44.PubMedCrossRef

37.

Zhu YJ, Liu SY, Wang H, Wei P, Ding XP. The prevalence of azoospermia factor microdeletion on the Y chromosome of Chinese infertile men detected by multi-analyte suspension array technology. Asian J Androl. 2008;10(6):873–81.PubMedCrossRef

Title: Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men
Authors: Li Fu
Da-Ke Xiong
Xian-Ping Ding
Chuang Li
Li-Yuan Zhang
Min Ding
Shuang-Shuang Nie
Qiang Quan
Publication date: 01-06-2012
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 6/2012
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-012-9741-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men

Abstract

Purposes

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purposes

Methods

Results

Conclusions

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