Abstract
The human androgen receptor gene (AR) is an important regulator of male sexual development including spermatogenesis. Exon 1 of this gene encodes the N terminal domain, which controls transcriptional activity of the receptor and the two polymorphic repeats CAG and GGN. Many studies have reported association of the expanded CAG repeat length with male infertility, although this is still controversial. The GGN repeat, in contrast, has been less thoroughly studied. Thus far, only scanty studies have been reported from African populations and none from Nigeria. Therefore, we have investigated the possible association between AR polymorphism repeats length (CAG and GGN) and reduced spermatogenesis in infertile Nigerian men (no.=60) consisting of 20 non-obstructive azoospermic and 40 oligozoospermic subjects compared with controls with normozoospermia and proven evidence of fertility (no.=38). In addition, 48 volunteers with normal spermatogenesis were recruited from a German population. CAG and GGN repeats length were determined by fragment length analysis using GeneScan. The CAG and GGN repeats length of infertile compared to fertile populations were not significantly different (p>0.05). We found a unique AR GGN allele distribution with 20–23 GGN repeats predominant in the Nigerian study population. Our results show that CAG and GGN repeats polymorphisms are not a critical index of male infertility. While we do not find a relationship with CAG and GGN repeats haplotypes and male infertility, we report for the first time a unique and wider distribution of the GGN allele in the Nigerian population which is significantly different from the Caucasian population. The functional relevance of this variance to male fertility warrants in-depth elucidation.
Similar content being viewed by others
References
Okonofua F. New reproductive technologies and infertility treatment in Africa. Afr J Reprod Health 2003, 7: 7–11.
Chukudebelu WO. The male factor in infertility — Nigerian experience. Int J Fertil 1978, 23: 238–9.
Esimai OA, Orji EO, Lasisi AR. Male contribution to infertility in IleIfe, Nigeria. Niger J Med 2002, 11: 70–2.
Samli H, Samli MM, SolakTM, Imirzalioglu N. Genetic anomalies detected in patients with non-obstructive azoospermia and oligozoospermia. Arch Androl 2006, 52: 263–7.
Foresta C, Ferlin A, Gianaroli L, Dalla Piccola B. Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet 2002, 10: 303–12.
Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet 2004, 364: 273–83.
Simoni M, Gromoll J, Dworniczak B, et al. Screening for deletions of the Y chromosome involving the DAZ (deleted in azoospermia) gene in azoospermia and severe oligospermia. Fertil Steril 1997, 67: 542–7.
Page DC, Silber S, Brown LG. Men with infertility caused by AZFc deletion can produce sons by intracytoplasmic sperm injection, but are likely to transmit the deletion and infertility. Hum Reprod 1999, 14: 1722–6.
Maurer B, Gromoll J, Simoni M, Nieschlag E. Prevalence of Y chromosome microdeletions in infertile men who consulted a tertiary care medical centre: the Münster experience. Andrologia 2001, 33: 27–33.
Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alteration of spermatogenesis. Endocr Rev 2001, 22: 226–39.
Krausz C, Fellous M. Chromosome Y and infertility in men. Ann Endocrinol (Paris) 2003, 64: 403–12.
Vogt PH. Azoospermia factor (AZF) in Yq11: towards a molecular understanding of its function for human male fertility and spermatogenesis. Reprod Biomed Online 2005, 10: 81–93.
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: 191–7.
Fernando L, Gromoll J, Weerasooriya TR, Nieschlag, Simoni M. Y-chromosomal microdeletions and partial deletions of the Azoospermia Factor c (AZFc) region in normozoospermic, severe oligozoospermic and azoospermic men in Sri Lanka. Asian J Androl 2006, 8: 39–44.
Gao T, Marcelli M, McPhaul MJ. Transcriptional activation and transient expression of the human androgen receptor. J Steroid Biochem Mol Biol 1996, 59: 9–20.
Asatiani K, von Eckardstein S, Simoni M, Gromoll J, Nieschlag E. CAG repeat length in the androgen receptor gene affects the risk of male infertility. Int J Androl 2003, 26: 255–61.
von Eckardstein S, Syska A, Gromoll J, Kamischke A, Simoni M, Nieschlag E. Inverse correlation between sperm concentration and number of androgen receptor CAG repeats in normal men. J Clin Endocrinol Metab 2001, 86: 2585–90.
Kittles R A, Young D, Weinrich S, Hudson J, Argyropoulos G, Ukoli F, Adams-Campbell Land Dunston GM. Extent of linkage equilibrium between the androgen receptor gene CAG and GGC repeats in human populations: implications for prostate cancer risk. Hum Genet 2001, 109: 253–61.
Lundin KB, Giwercman YL, Rylander L, Hagmar L, Giwercman A. Androgen receptor gene GGN repeats length and reproductive characteristics in young Swedish men. Eur J Endocrinol 2006, 155: 347–54.
Rajender S Rajani V, Gupta NJ, Chakravarty B, Singh L, Thangaraj K. No association of androgen receptor GGN repeat length polymorphism with infertility in Indian men. J Androl 27: 785–9.
Ferlin A Bartoloni L Rizzo G Roverato A Garolla A, Foresta C. Androgen receptor gene CAG and GGN repeats lengths in idiopathic male infertility. Mol Hum Reprod 2004, 10: 417–21.
Ruhayel Y, Lundin K, Giwercman Y, Halldén C, Willén M, Giwercman A. Androgen receptor gene GGN and CAG polymorphisms among severely oligozoospermic and azoospermic Swedish men. Hum Reprod 2004, 19: 2076–83.
Saare M, Belousova A, Punab M, et al. Androgen receptor gene haplotype is associated with male infertility. Int J Androl 2008, 31: 395–402.
Tüttelmann F, Luetjens CM, Nieschlag E. Optimising workflow in andrology: a new electronic patient record and database. Asian J Androl 2006, 8: 235–41.
World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interactions. 4th ed. Cambridge/New York: Cambridge University Press, 1999.
Dadze S, Wieland C, Jakubiczka S, Funke E, Schröder E. The size of CAG repeats in exon 1 of the androgen receptor gene expression shows no significant relationship to impaired spermatogenesis in an infertile Caucasoid sample of German origin. Mol Hum Reprod 2000, 6: 207–14.
Dhillon VS, Husain SA. Cytogenetic and molecular analysis of the Y chromosome: absence of a significant relationship between CAG repeat length in exon 1 of the androgen receptor gene and infertility in Indian men. Int J Androl 2003, 26: 286–95.
Thangaraj K, Joshi M, Reddy AG, Gupta NJ, Chakravarty B, Singh L. CAG repeat expansion in the androgen receptor gene is not associated with infertility in Indian population. J Androl 2002, 23: 815–8.
Hadjkacem L, Hadj-Kacem H, Boulila A, Bahloul A, Ayadi H, Ammar-Keskes L. Androgen receptor gene CAG repeats length in fertile and infertile Tunisian men. Ann Genet 2004, 47: 217–24.
Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrin Metab 2007, 92: 4319–26.
Tut TG, Ghadessy FJ, Trifiro MA, Pinsky L, Yong EL. Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab 1997, 82: 3777–82.
Aschim EL, Nordenskjöld A, Giwercman A, et al. Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene. J Clin Endocr Metab 2004, 89: 5105–09.
Radpour R, Rezaee M, Tavasoly A, Solati S, Saleki A. Association of long polyglycine tracts (GGN repeats) in exon 1 of the androgen receptor gene with cryptorchidism and penile hypospadias in Iranian patients. J Androl 2007, 28: 164–9.
Hillmer AM, Hanneken S, Ritzmann S, et al. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am J Hum Genet 2005, 77: 140–8.
Irvine RA, Yu MC, Ross RK, Coetzee GA. The CAG and GGC microsatellites of the androgen receptor gene is in linkage disequilibrium in men with prostate cancer. Cancer Res 1994, 55: 1937–40.
Sartor O, Zheng Q, Eastham JA. Androgen receptor gene CAG repeat length varies in a race-specific fashion in men without prostate cancer. Urology 1999, 53: 378–80.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Akinloye, O., Gromoll, J., Nieschlag, E. et al. Androgen receptor gene CAG and GGN polymorphisms in infertile Nigerian men. J Endocrinol Invest 32, 797–804 (2009). https://doi.org/10.1007/BF03345748
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03345748