Ebru ETEM, Faruk KUYUCU, Arslan ARDIÇOĞLU, Hüseyin YÜCE

İnfertilite ve anormal semen analizleri gösteren erkeklerde FSHR Ala189Val gen polimorfizminin analizi

Amaç: Follikül stimüle edici hormon (FSH) hormonu dişilerde follikulogenezis ve erkeklerde spermatogenezisde temel rol oynamaktadır. Erkekte FSH yetişkinlerde spermatogenezisin pubertal başlamasında ve kantitatif olarak normal sperm üretiminin korunmasında görevlidir. Follikül stimüle edici hormon reseptör (FSHR) geninde aktivasyon ve inaktivasyon mutasyonları tanımlanmıştır. 566C→T mutasyonu reseptör molekülünün ekstrasellüler alanını kodlayan bölgede olup FSHR geninin ekzon 7�sinde lokalizedir. Fonksiyonel testler mutasyonlu reseptör tarafından ligand bağlanması ve sinyal iletiminin azaldığını göstermektedir. Çalışmanın amacı Dünya Sağlık Örgütü (DSÖ) kriterlerine göre, aynı laboratuar teknisyeni tarafından spermiogram tetkikleri değerlendirilen 80 oligospermik hastada FSHR genindeki Ala189Val mutasyonunu incelemektir. Gereç ve Yöntem: FSHR geninin ekzon 7�sindeki Ala189Val mutasyonu Restriksiyon Fragment Uzunluk Polimorfizm (RFLP) yöntemi kullanılarak analiz edildi. Bulgular: Homozigot veya heterozigot mutasyonlar tanımlanamamıştır. Sonuç: Değerlendirilen hastaların sayısı küçük olmasına rağmen Fin populasyonu dışında tüm diğer populasyon raporları göz önünde bulundurulduğunda bu gendeki Ala189Val mutasyonunun sıklığı oldukça düşüktür. FSHR�deki Ala189Val mutasyonu oligospermili infertil Türk erkeklerde yaygın değildir. Bu sonuçlar FSHR genindeki C566T mutasyonunun Finlandiya'da yaygın ancak diğer populasyonlarda yaygın olmadığını desteklemektedir

Anahtar Kelimeler:

Oligospermi, Folikül uyarıcı hormon, Semen analizi, Reseptörler, FSH, Polimorfizm, genetik, Kısırlık, erkek

FSHR Ala189Val gene polymorphisms in men presenting with infertility and abnormal semen analysis

Objective: The follicle-stimulating hormone (FSH) is considered essential for folliculogenesis in the female and spermatogenesis in the male. In the male, FSH is generally considered essential for the pubertal initiation of spermatogenesis and maintenance of quantitatively normal sperm production in adults. Mutations of the the follicle stimulating hormone receptor (FSHR) leading to either constituve activation or inactivation of the receptor have been identified. The 566C→T mutation, predicting an alanine to valine substitution, is located in exon 7 of the FSHR gene, in the region encoding the extracellular domain of the receptor molecule. Functional testing showed a clear-cut reduction in ligand binding and signal transduction by the mutated receptor. The purpose of the present study was to investigate in 80 patients with oligospermia which spermiograms were performed according to World Health Organization (WHO) quidelines by the same biologist to presented Ala189Val mutation in the FSHR gene. Materials and Methods: Ala189Val mutation in the exon7 of the FSHR gene analyzed by Restriction Fragment Lenght Polymorphism (RFLP) method. Results: No heterozygous or homozygous mutant alleles were present in any of the patients. Conclusion: Although the number of patients evaluated was small, considering all other previous reports, it seems that except in the Finnish population, proportion of men with Ala189Val mutation in this gene is very low. The Ala189Val mutation of FSHR is not a common polymorphism in Turkish infertil men with oligospermia. These results suggest that the C566T mutation of the FSHR gene is enriched Finland, but is uncommon in other population.

Keywords:

Oligospermia, Follicle Stimulating Hormone, Semen Analysis, Receptors, FSH, Polymorphism, Genetic, Infertility, Male,

PDF

___

1) World Health Organization: WHO Laboratory Manual for the Examination of Human Semen and Sperm- Cervical Mucus Interaction. Cambridge, England, Cambridge University Pres, 1999.
2) Allan CM, Garcia A, Spaliviero J. Complete Sertoli cell proliferation induced by follicle-stimulating hormone (FSH) independently of luteinizing hormone activity: evidence from genetic models of isolated FSH action. Endocrinology 2004; 4: 1587-1593.
3) Vaskivuo TE, Aittomaki K, Anttonen M. Effects of folliclestimulating hormone (FSH) and human chorionic gonadotropin in individuals with an inactivating mutation of the FSH receptor. Fertil Steril 2002; 78: 108-113.
4) Baccetti B, Collodel G, Costantıno-Ceccarını E. Localization of human follicle-stimulating hormone in the testis. FASEB J 1998; 2: 1045-1054.
5) Tapanainen JS, Aittomaki K, Min J, Vaskivuo T, Huhtaniemi IT. Men homozygous for an inactivating mutation of the folliclestimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nat Genet 1997; 2: 205-206.
6) Layman LC, Amde S, Cohen DP, Jin M, Xie J. The Finnish follicle-stimulating hormone receptor gene mutation is rare in North American women with 46,XX ovarian failure. Fertil Steril 1998; 2: 300-302.
7) Allen LA, Achermann JC, Pakarinen P. A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics. Hum Reprod 2003; 2: 251-256.
8) Kohek MB, Batista MC, Russell AJ. No Evidence of the inactivating mutation (C566T) in the follicle-stimulating hormone receptor gene in Bralizilian women with premature ovarian failure. Fertil Steril 1998; 70: 565-567.
9) Gromoll J, Simoni M, Nıeschlag E. An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man. J Clin Endocrinol Metab 1996; 81: 1367-1370.
10) de la Chesnaye E, Canto P, Ulloa-Aguirre A, Mendez JP. No evidence of mutations in the follicle-stimulating hormone receptor gene in Mexican women with 46,XX pure gonadal dysgenesis. Am J Med Genet 2001; 2: 125-128.
11) Jiang M, Aittomaki K, Nilsson C. Huhtaniemi I. The frequency of an inactivating point mutation (566C→T) of the human folliclestimulating hormone receptor gene in four populations using allele-specific hybridization and time-resolved fluorometry. J Clin Endocrinol Metab 1998; 12: 4338-4343.