Turkiye"nin Çukurova Bölgesinde İnfertil Erkeklerde Y Kromozom Mikrodelesyonlarının Saptanması

Safiye Taga; Hulya Leventerler; Abdullah Tuli; İbrahim Ferhat Ürünsak; İbrahim Atilla Arıdoğan; Nesrin Ercelen; Suna Solmaz; Mehmet Turan Çetin; Nurten Dikmen

EN TR

Determination of Y Chromosome Microdeletions in Infertile Men at The Cukurova Region in Turkey

Abstract

Purpose:Y Chromosome infertility is inherited in a Y-linked manner. Three different regions have been mapped on the long arm of the Y chromosome, named ""Azoospermic Factor"" (AZFa, AZFb and AZFc) are involved in the control of spermatogenesis. Microdeletions in these gene loci may result in azoospermia or severe oligozoospermia. The aim of this study is to establish the prevalence of Y chromosomal microdeletions in infertile men at the Cukurova Region in Turkey. Material and Methods: We evaluated the frequency of Y chromosome deletions in 63 infertile men (38 azoospermic and 25 severe oligozoospermic) and 10 fertile men as a control group by using multiplex polymerase chain reaction (PCR) analyis. Plasma hormone concentrations of all patients including FSH, LH, testosterone, prolactin and leptin were measured by radioimmunoassay Results: Microdeletion frequency detected in all cases was 6.3% (4/63). The values for azoospermic group and severe oligozoospermic group were 7.8% (3/38) and 4% (1/25) respectively. Deletions were found at AZFb, AZFc and proximal AZFc/d regions in infertile group. However, no microdeletions were detected at the AZFa region. No deletions were found in the control group. FSH and LH levels were significantly elevated in azoospermic group than control and severe oligozoospermic groups (p:0.000). Prolactin levels were significantly elevated in azoospermic group than control group (p:0.000). Conclusion:Detection of Y Chromosome deletions in infertile males in routine clinical diagnosis may suitable for counseling prior to assisted reproduction.

Keywords

Y chromosome microdeletions, male infertility, AZF genes, PCR

Turkiye"nin Çukurova Bölgesinde İnfertil Erkeklerde Y Kromozom Mikrodelesyonlarının Saptanması

Öz

Amaç: Y kromozomuna bağlı infertilite Y-bağlı kalıtım gösterir. Y kromozomunun uzun kolunda, spermatogenezden sorumlu ""Azospermik Faktör"" olarak anılan, AZFa, AZFb ve AZFc şeklinde üç farklı bölge tanımlanmıştır. Bu bölgelerin delesyonu azospermi ya da şiddetli oligospermi ile sonuçlanabilmektedir. Bu çalışmanın amacı, Türkiye"nin Çukurova Bölgesi"ndeki infertil erkeklerde Y kromozom mikrodelesyon sıklığının saptanmasıdır. Materyal ve Metod: Çalışmada, 63 infertil erkekte (38 azospermik, 25 şiddetli oligospermik) ve 10 fertil kontrol grubunda Y kromozom mikrodelesyonu multipleks PCR yöntemi ile araştırılmıştır. Tüm olguların plazma FSH, LH, testosteron, prolaktin ve leptin düzeyleri "radiyoimmünoassay" yöntemiyle çalışılmıştır. Bulgular: Mikrodelesyon görülme sıklığı tüm olgularda %6,3 (4/63) iken, azospermik grupta %7,8 (3/38), şiddetli oligospermik grupta %4 (1/25) bulunmuştur. İnfertil grupta, AZFb, AZFc ve proksimal AZFc/d bölgelerinde mikrodelesyon saptanırken AZFa bölgesinde delesyon saptanmamıştır. Kontrol grubunda delesyon görülmemiştir. Azospermik grupta FSH ve LH düzeyleri şiddetli oligospermik ve kontrol gruplarına göre anlamlı derecede yüksek bulunmuştur (p.0000). Azospermik grupta prolaktin düzeyi kontrol grubuna göre yüksek saptanmıştır (p:000). Sonuç: İnfertil erkeklerin rutin klinik tanısında, Y kromozom mikrodelesyonlarının tayini, yardımcı üreme yöntemlerinden önce danışmanlık amaçlı kullanılabilir.

Anahtar Kelimeler

Y kromozom mikrodelesyonları,erkek infertilitesi, AZF genleri, PCR

Kaynakça

Skakkebaek NE, Giwereman A, de Kretser D. Pathogenesis and management of male infertility. Lancet.1994; 343:1473-4.
Revelli A, Tur Kasoa I, Holte JG, Massobrio M: Biotechnology of Human Reproduction. Parthenon Publishing, 2003.
Delbridge ML, Marshall Graves JA. Mammalian Y chromosome evolution and the male-spesific functions of Y chromosome-borne genes. Rev Reprod. 1999; 4:101-9.
Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s sydrome. Lancet. 2004; 364:273-83.
Sher A, Hasnain SE. Molecular dissection of the human Y-chromosome. Gene. 2002; 283:1-10.
Sher A, Hasnain SE. Genomics of the human Ychromosome 1.Association with male infertility. Gene. 2003; 321:25-37.
Quintana-Murci L, Krausz C, McElreavey K. The human y chromosome. function, evolution and disease. Forensic Sci Int. 2001; 118:169-81.
Van der Ven K, Montag M, Preschka B, Leygraal J, Scwanitz G, Haidi G et al. Combined cytogenetic and Y chromosome microdeletion screening in males undergoing intracytoplasmic sperm injection. Mol Hum Reprod. 1997;3:699-704.
Kremer JAM, Tuerlings JHAM, Meuleman EJH, Schoute F, Mariman E, Smeets DFCM et al. Microdeletions of the Y chromosome and intracytoplasmic sperm injection: from gene to clinic. Hum Reprod. 1997;12:687-91.
Olivia R, Margarit E, Ballesca JL, Carrio A, Sanchez A, Mila M et al. Prevalence of Y chromosome microdeletions in oligospermic and azoospermic candidates for intracytoplasmic sperm injection. Fertil Steril. 1998;70:506-10.

Silber SJ, Alagappan R, Brown LG, Page DC. Y chromosome deletions in azospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction. Hum Reprod.1998; 13:332-7.
Van Golde RJT, Wetzels AMM, Graaf R, Tuerlings JHAM, Braat DDM, Kremer JAM. Decreased fertilization rate and embryo quality after ICSI in oligozoospermia factor c region of the Y chromosome. Hum Reprod. 2001;16:289-92.
Gianotten J, Hoffer JVM, De Vries JWA, Leschot NJ, Gerris J, Van der Veen F. Partial DAZ deletion in a family with five infertile brothers. Fertil Steril. 2003; 79:1652-5.
Lahn BT, Page D. Functional coherence of the human Y chromosome. Science. 1997; 278:675-9.
Cooke, J H. Y Chromosome and male infertility. Rev Reprod. 1999; 4:5- 10.
Krausz C and McEreavey.Y chromosome and male infertility. Front Biosci.1999; 15:1-8.
Foresta C, Ferlin A, Moro E. Deletion and expression analysis of AZFa genes on the human chromosome revealed a major role for DBY in male infertility. Hum Mol Genet. 2000;9:1161-9.
Foresta C, Moro E, Ferlin A: Y chromosome microdeletions and alterations of spermatogenesis. Endoc Rev. 2001; 22:226-39.
Affara NA. The role of the Y chromosome in male infertility. Exp rev mol med. 2001; 3:1-16.
Leventerler H, Dikmen N. Y Kromozomu. Ç.Ü. Arşiv Dergisi. 2002; 11: 321-34.
Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet. 1976; 34:119-24.
Reijo R, LeeT-Y, Salo P, Alagappan R, Brown LG, Rosenberg M et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genet.1995; 10:383-93.
Vogt PH, Edelman A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996; 5:933-49.
Najmabadi H, Huang V, Yen P, Subbarao MN, Bhasin D, Banaag L et al. Substantial prevalence of microdeletions of the Y-Chromosome in infertile men with idiopathic azoospermia and oligozoospermia detected using a squence-tagged site-based mapping strategy. J Clin Endocrinol Metab. 1996: 81:1347-52.
Kent-First M, Muallem A, Shultz J, Pryor J, Roberts K, Nolten W et al. Defining regions of the YChromosome responsible for male infertility and identification of a fourth AZF Region (AZFd) by Ychromosome microdelection detection. Mol Reprod Develop. 1999; 53:27-41
Krausz K, Forti G, McElreavey. The Y chromosome and male fertility and infertility Int J Androl. 2003; 26:670-75.
Ferlin A, Moro E, Garolla A, Foresta C. Human male infertility and Y chromosome deletions: role of thecandidate genes DAZ, RBM and DFFRY. Hum Reprod. 1999; 14:1710-16.
Ferlin A, Moro E, Onisto M, Toscana E, Bettella A, Foresta C. Absence of testicular DAZ gene expression in idiopathic severe testiculopathies. Hum Reprod.1999; 14:2286-92.
Fox M S, Pera RAR. Male infertility, genetic analysis of DAZ genes on human Y chromosome and genetic analysis of DNA repair. Mol Cell Endocrinol. 2001; 184:41-9.
Ditton HJ, J Zimmer, C Kamp, E Rajpert-De Meyts, PH Vogt. The AZFa gene DBY (DDX3Y) is wiedly transcribed but the protein is limited to the male germ cells by translation control. Hum Mol Genet. 2004; 13:2333-41.
Kuo PL, Lın YH, Teng YN, Hsu CC, Lın JSN, Lın YM. Transcriptional levels of four Y chromosome-linked AZF genes in azoospermic men and their association with succesful sperm retrieval. Urology. 2004; 63:131-6.
Girardi SK, Mielnik A, Schlegel PN. Submicroscopic deletions in the Y chromosome of infertile men. Hum Reprod. 1997:12: 1635-41.
Foresta C, Ferlin A, Andrea G, Rossato M, Barbaux S, Bortoli A. Y chromosome deletions in idiopathic severe testiculopathies. J Clin Endocrinol Metab.1997; 82:1075-9.
Foresta C, Ferlin A, Garolla A, Moro E, Pistorella M, Barbaux S et al. High frequency of well-defined Ychromosome deletions in idiopathic Sertoli cell-only syndrome. Hum Reprod.1998;13:302-7.
Brandel RA, Mielnik A, Liotta D, Ye Z, Veeck LL, Palermo GD et al. AZFb deletions predict the absence of spermatozoa with testicular sperm extraction: preliminary report of a prognostic genetic test. Hum Reprod. 1998; 133: 2812-15.
Martinez MC, Bernabe MJ, Gomez E, Ballesteros A, Landers J, Glover G et al. Screening for AZF deletion in large series of severely impaired spermatogenesis patients. J Androl. 2000; 21:651-55.
Kamp C, Huellen K, Fernandes S, Sousa M, Schlegel PN, Mielnik A et al. High deletion frequency of the complete AZFa sequence in men with Sertolicell-only syndrome. Mol Hum Reprod. 2001; 7:987
Hopps CV, Mielnik A, Goldstein M, Palermo GD, Resenwaks Z, Schlegel PN. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum Reprod. 2003; 18:1660-5.
Chiang H-S, Yeh S-D, Wu C-C, Huang B-C, Tsai HJ, Fang C-L. Clinical and pathological correlation of the microdeletion of Y chromosome for the 30 patients with azoospermia and severe oligoasthenospermia. Asian J Androl. 2004; 6:369
Krausz C, Quintana-Murci L, Barbaux S, Siffroi JP, Rouba H, Delafontaine D et al. A high frequency of Y chromosome deletions in males with nonidiopathic infertility. J Clin Endocrinol Metab.1999; 84:3606-12
Peterlin B, Kunej T, Sinkovec J, Gligorievska N, Zorn B. Screening for Y chromosome microdeletions in 226 Slovenian subfertile men. Hum Reprod. 2002; 17:17-24.
Ioulıanos A, Sısmanı C, Fourouclas N, Patroclou T, Sergıo C, Patsalıs PC. A nation-based population screening for azoospermia factor deletions in GreekCypriot patients with severe spermatogenic failure and normal fertile controls, using a spesific study and experimental design. Int J Androl. 2002; 25:53-8.
Kunej T, Zorn B, Peterlin B. Y chromosome microdeletion in infertile men with cryptorchidism. Fertil Steril. 2003; 79:1559-65.
Thangaraj K, Gupta NJ, Pavani K, Reddy AG, Subramaınan S, Rani DS et al. Y chromosome deletions in azoospermic men in India. J Androl. 2003; 24: 588-97.
Telöken C, Arent A, Chammas M, Bertaiolli V, Marques DS, Badalotti M. Microdeletions of Y chromosome genes in infertile men. Elsevier İnternational Congress Series. 2004; 1271:173-6.
Song NH, Wu HF, Zhang W, Zhuo ZM, Qian LX, Hua LX, Guo L, Feng NH. Screening for Y chromosome microdeletions in idiopathic and nonidiopathic infertile men with varicocele and cryptorchidism. Chin med J. 2005; 118:1462-7.
Stouffs K, Lissens W, Tournaye H, Steirteghem AV, Liebaers İ. The choice and outcome of the fertility tratment of 38 couples in whom the male partner has a Yq microdeletion. Hum Reprod. 2005; 20:1887-96.
Medika I, Gligorievska N, Prenc M, Peterlin B. Y microdeletions in the Istria county, Croatia. Asian J Androl. 2005; 7:213-6.
Abdelmoula NB, Sallami A, Chackroun N, Keskes L, Amouri A. Evaluation of DAZ microdeletions in 34 infertile men. Arch Andrology. 2006; 52:175-8.
Hadj-Kacem L, Hadj-Kacem H, Ayadi H. Screening of the Y chromosome microdeletions in Tunisian infertile men. Arch Andrology. 2006; 52:169-74.
Fernando L, Gromol J, Weerasooriya TR, Nieschlag E, Simoni M. Y-chromosomal microdeletions and partial deletions of theAzospermia Factor c (AZFc) region in normospermic, severe oligospermic and azoospermic men in Sri Lanka. Asian J Androl. 2006; 8:39-44.
Imken L, El Houate B, Chafik A, Nahili H, Boulouiz R, Abidi O et al. AZF microdeletions and partial deletions of AZFc region on the Y chromosome Moroccan men. Asian J Androl. 2007; 9:674-8.
Simoni M. Molecular diagnosis of Y chromosome microdeletions in Europa: state-of-the-art and quality control. Human Reprod. 2001;16:402-9.
Simoni M, Bakker E, Krausz C. EAA/EMQN best practice gudelines for molecular diagnosis of ychromosomal microdeletions State of the art 2004. Int J Androl. 2004; 27: 240-9.
Yüreğir GT, Donma O, Dikmen N, Isbir T, Cınar M. Population studies of Hemoglobin S and other variants in Çukurova, the southhern part of Turkey. Acta Haematol. 1987; 50:757-65.
Yüreğir GT, Donma O, Dikmen N, Isbir T, Cınar M. Population studies of Hemoglobin S and other variants in Çukurova, the southhern part of Turkey:need for prenatal diagnosis. Ann Med Sci. 1995; 4:61-9.
Altay C. Abnormal hemoglobins in Turkey. Turkish J Haematol. 2002; 19:63-74.
Ma K, Inglis JD, Sharkey A, Bickmore WA, Hill RE , Prosser EJ et al. A Y chromosome gene family with RNA-binding protein homology: Candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell. 1993; 77:1287-95.
Kostiner DR, Turek PJ, Reijo RA. Male infertility: analysis of the markers and genes on human Y chromosome. Hum Reprod.1998; 13:3032-8.
Oates RD, Silber S, Brown LG., Page, DC. Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod. 2002; 17:2813-24.
Okutman-Emonts O, Pehlivan S, Tavmergen E, Tavmergen-Göker EN, Ozkinay F. Screening of Ychromosome microdeletion which contains AZF regions in 71 Turkish azoospermic men. Genet Couns. 2004; 15:199-205.
Vicdan A, Vicdan K, Günalp S, Kence A, Akarsu C, Işık AZ et al. Genetic aspects of human male infertility: the freguency of chromosomal abnormalities and Y chromosome microdeletions in severe male actor infertility.Obstetrıcs and Gynecology. 2003;1-6.
Sevinç D, Zehir A, Biricik A, Sertyel S, Kahraman S, Güney İ. Relation beetween human Y chromosome microdeletions and sperm morphology. Marmara Medical Journal. 2002; 15:227-32.
Krausz C, Quintana Murci L, Sayar H, McElreavey K. AZF gene-spesific screening in highly selected Iranian patients. Abstracts of the 18th Annual Meeting of ESHRE, Vienna, Austria 2002. Hellani A, AlHassan S, Iqbal MA, Coşkun S. Y chromosome microdeletions in infertile men with idiopathic oligo/or azospermia. J Exp Clin Assist Reprod. 2006; 3:1743-50.
Mitra A, Dada R, Kumar R, Grupta NP, Kucheria K, Grupta SK. Screening for Y-chromosome microdeletions in infertile Indian males: Utility of simplified multiplex PCR. Indian J Med Res. 2008; 127:124-32.
Kleiman SE, Almog R, Yogev L, Hauser R, Lehavi O, Paz Gedalia et al. Screening for partial AZFa microdeletions in the Y chromosome of infertile men: is it of clinical relevance?. Andrology. 2012; 98:43-7.
Tomasi PA, Oates R, Brown L, Deliata G, Page DC. The pituitary-Testicular axis in Klinefelter’s sydrome and in oligo-azoospermic patients with and withouth deletions of the Y chromosome long arm. Clin Endocrinol (Oxf). 2003; 59:214-22.
Yazışma Adresi / Address for Correspondence: Uz. Safiye Taga Cukurova Faculty of Medicine, Gynecology and Obstetric Department-Center of Assisted Reproduction 01330 Balcalı-ADANA e-mail: staga@cu.edu.tr geliş tarihi/received :11.04.2013 kabul tarihi/accepted:17.05.2013

Ayrıntılar

Birincil Dil

Türkçe

Konular

-

Bölüm

-

Yazarlar

Safiye Taga Bu kişi benim

Hulya Leventerler Bu kişi benim

Abdullah Tuli Bu kişi benim

İbrahim Ferhat Ürünsak Bu kişi benim

İbrahim Atilla Arıdoğan Bu kişi benim

Nesrin Ercelen Bu kişi benim

Suna Solmaz Bu kişi benim

Mehmet Turan Çetin Bu kişi benim

Nurten Dikmen Bu kişi benim

Yayımlanma Tarihi

1 Aralık 2013

Gönderilme Tarihi

22 Temmuz 2014

Kabul Tarihi

-

Yayımlandığı Sayı

Yıl 1970 Cilt: 38 Sayı: 4

IZ

https://izlik.org/JA86RU84SD

MLA

Taga, Safiye, vd. “Turkiye"nin Çukurova Bölgesinde İnfertil Erkeklerde Y Kromozom Mikrodelesyonlarının Saptanması”. Cukurova Medical Journal, c. 38, sy 4, Aralık 2013, ss. 723-3, https://izlik.org/JA86RU84SD.

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Determination of Y Chromosome Microdeletions in Infertile Men at The Cukurova Region in Turkey

Abstract

Keywords

Turkiye"nin Çukurova Bölgesinde İnfertil Erkeklerde Y Kromozom Mikrodelesyonlarının Saptanması

Öz

Anahtar Kelimeler

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

IZ

Kaynak Göster