Biopolym. Cell. 2008; 24(3):231-237.
Analysis of defects in the AZF gene of the Y-chromosome and the CFTR gene involved in male infertility
1Fesai O. A., 1Pampukha V. M., 1Solovyov O. O., 1Livshits L. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


Microdeletions of the long arm of the human Y chromosome are associated with spermatogenic failure and have been used to define three regions of Yq (AZFa, AZFb and AZFc) that are recurrently deleted in infertile males. Microdeletions were detected in 16 out of 355 (4,5 %) infertile males. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, also involved in male infertility, were detected in 22 out of 355 analyzed infertile males. The most common mutation was F508del (17 of 22 mutations). 5T allele of the CFTR gene associated with congenital bilateral absence of the vas deferens was detected in 16 out of 355 (4,5 %) patients. Molecular-genetic analysis of the Y-chromosome microdeletions and the CFTR gene mutations as well as genetic counseling are the necessary diagnostics for patients with male infertility, especially if they are included in an assisted reproductive technologies program.
Keywords: spermatogenesis, Y-chromosome microdeletions, CFTR gene, male infertility


[1] Krausz C, Quintana-Murci L, Barbaux S, Siffroi JP, Rouba H, Delafontaine D, Souleyreau-Therville N, Arvis G, Antoine JM, Erdei E, Taar JP, Tar A, Jeandidier E, Plessis G, Bourgeron T, Dadoune JP, Fellous M, McElreavey K. A high frequency of Y chromosome deletions in males with nonidiopathic infertility. J Clin Endocrinol Metab. 1999;84(10):3606-12.
[2] Diemer T, Desjardins C. Developmental and genetic disorders in spermatogenesis. Hum Reprod Update. 1999;5(2):120-40.
[3] Vogt PH. Human chromosome deletions in Yq11, AZF candidate genes and male infertility: history and update. Mol Hum Reprod. 1998;4(8):739-44.
[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):119-24.
[5] Affara NA. The role of the Y chromosome in male infertility. Expert Rev Mol Med. 2001;2001:1-16.
[6] Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, Kohn FM, Schill WB, Farah S, Ramos C, Hartmann M, Hartschuh W, Meschede D, Behre HM, Castel A, Nieschlag E, Weidner W, Gr?ne HJ, Jung A, Engel W, Haidl G. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996;5(7):933-43.
[7] Habermann B, Mi HF, Edelmann A, Bohring C, B?ckert IT, Kiesewetter F, Aum?ller G, Vogt PH. DAZ (Deleted in AZoospermia) genes encode proteins located in human late spermatids and in sperm tails. Hum Reprod. 1998;13(2):363-9.
[8] Cooke HJ, Elliott DJ. RNA-binding proteins and human male infertility. Trends Genet. 1997;13(3):87-9.
[9] van der Ven K, Messer L, van der Ven H, Jeyendran RS, Ober C. Cystic fibrosis mutation screening in healthy men with reduced sperm quality. Hum Reprod. 1996;11(3):513-7.
[10] Erlich H. A. PCR technology: principles and applications for DNA amplification. New York: Stockton press, 1989. 207 p.
[11] Livshyts' LA. A molecular genetic analysis of the mutations in the exons of the CFTR gene in cystic fibrosis patients in Ukraine. Tsitol Genet. 2000;34(4):6-9.
[12] Livshyts' L. A., Nechyporenko M. V., Yasins'ka O. A., Pampukha V. M., Hryshchenko N. V., Kravchenko S. A., Livshyts' H. B., Sudoma I. V., Zinchenko V . M. Genetic testing programs assisted reproductive technologies. Zb. nauk. prats' akademiyi spivrobitnykiv KMAPO im. P. L. Shupika. Kyyiv, 2004. 5(13):356.
[13] Le Bourhis C, Siffroi JP, McElreavey K, Dadoune JP. Y chromosome microdeletions and germinal mosaicism in infertile males. Mol Hum Reprod. 2000;6(8):688-93.
[14] Zamani A. G., Kutlu R., Durakbasi-Dursun H. G., Gorkemli H., Acar A. Y chromosome microdeletions in Turkish infertile men. Ind. J. Hum. Genet. 2006. 12(2):66–71.
[15] Chernykh VB, Chukhrova AL, Beskorovanaia TS, Grishina EM, Sorokina TM, Shileko LV, Gogolevskii PA, Kalugina AS, Morina GV, Togobetskii AS, Tanevskii VE, Zdanovskii VM, Gogolevskaia IK, Kramerov DA, Poliakov AV, Kurilo LF. Types of Y chromosome deletions and their frequency in infertile men. Genetika. 2006;42(8):1130-6.
[16] Kihaile PE, Yasui A, Shuto Y. Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin. J Exp Clin Assist Reprod. 2005;2:9.
[17] Medica I., Gligorievska N., Prenc M., Peterlin B. Y microdeletions in the Istra country, Croatia. As. J. Androl. 2005; 7(2):213–216.
[18] Bobadilla JL, Macek M Jr, Fine JP, Farrell PM. Cystic fibrosis: a worldwide analysis of CFTR mutations--correlation with incidence data and application to screening. Hum Mutat. 2002;19(6):575-606.
[19] Groman JD, Hefferon TW, Casals T, Bassas L, Estivill X, Des Georges M, Guittard C, Koudova M, Fallin MD, Nemeth K, Fekete G, Kadasi L, Friedman K, Schwarz M, Bombieri C, Pignatti PF, Kanavakis E, Tzetis M, Schwartz M, Novelli G, D'Apice MR, Sobczynska-Tomaszewska A, Bal J, Stuhrmann M, Macek M Jr, Claustres M, Cutting GR. Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. Am J Hum Genet. 2004;74(1):176-9.
[20] Gervais R, Dumur V, Rigot JM, Lafitte JJ, Roussel P, Claustres M, Demaille J. High frequency of the R117H cystic fibrosis mutation in patients with congenital absence of the vas deferens. N Engl J Med. 1993;328(6):446-7.