This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by von Eckardstein, S. Articles by Nieschlag, E. Search for Related Content PubMed PubMed Citation Articles by von Eckardstein, S. Articles by Nieschlag, E.

Inverse Correlation between Sperm Concentration and Number of Androgen Receptor CAG Repeats in Normal Men¹

Institute of Reproductive Medicine, University of Münster, D-48129 Münster, Germany

Address all correspondence and requests for reprints to: Prof. Dr. E. Nieschlag, F.R.C.P., Institute of Reproductive Medicine, University of Münster, Domagkstrasse 11, D-48129 Münster, Germany. E-mail: nieschl{at}uni-muenster.de

Abstract

Androgens are essential for the maintenance of normal spermatogenesis. Androgen action is mediated by the androgen receptor (AR), which in the testis is expressed by Leydig, peritubular, and Sertoli cells. The fact that sperm numbers range from 20 up to 300 million/mL in normal men without any indication of changed endocrine parameters led us to assume that genetic variability of transduction of androgen signaling could be important. We therefore compared the variable number of CAG repeats in the AR with sperm concentrations in men with normal ejaculate parameters (62 fathers and 69 volunteers participating in clinical trials). In multivariate analysis CAG repeat length did not differ between the volunteers (19.4 ± 3.1) and the fathers (20.6 ± 3.0), but was significantly correlated to sperm concentrations with a coefficient of -0.25. When compared with a group of infertile men with (n = 14) or without (n = 30) a family history of infertility, no such correlation was found. These results indicate that men with short CAG repeats have the highest sperm output within the normal fertile population. Polymorphisms of the AR contribute to the efficiency of spermatogenesis in normal men, but do not play a predominant role in male infertility.

This article has been cited by other articles:

				C. A. Davis-Dao, E. D. Tuazon, R. Z. Sokol, and V. K. Cortessis Male Infertility and Variation in CAG Repeat Length in the Androgen Receptor Gene: A Meta-analysis J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4319 - 4326. [Abstract] [Full Text] [PDF]

				E. Rajpert-De Meyts Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects Hum. Reprod. Update, May 1, 2006; 12(3): 303 - 323. [Abstract] [Full Text] [PDF]

				E. Guarducci, F. Nuti, L. Becherini, M. Rotondi, G. Balercia, G. Forti, and C. Krausz Estrogen receptor {alpha} promoter polymorphism: stronger estrogen action is coupled with lower sperm count Hum. Reprod., April 1, 2006; 21(4): 994 - 1001. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson, P. G. Stanton, L. O'Donnell, S. J. Meachem, J. K. Amory, R. Berger, W. J. Bremner, and R. I. McLachlan Effects of Testosterone and Levonorgestrel Combined with a 5{alpha}-Reductase Inhibitor or Gonadotropin-Releasing Hormone Antagonist on Spermatogenesis and Intratesticular Steroid Levels in Normal Men J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5647 - 5655. [Abstract] [Full Text] [PDF]

				A. Ferlin, A. Garolla, A. Bettella, L. Bartoloni, C. Vinanzi, A. Roverato, and C. Foresta Androgen receptor gene CAG and GGC repeat lengths in cryptorchidism Eur. J. Endocrinol., March 1, 2005; 152(3): 419 - 425. [Abstract] [Full Text] [PDF]

				K. L. Matthiesson, J. K. Amory, R. Berger, A. Ugoni, R. I. McLachlan, and W. J. Bremner Novel Male Hormonal Contraceptive Combinations: The Hormonal and Spermatogenic Effects of Testosterone and Levonorgestrel Combined with a 5{alpha}-Reductase Inhibitor or Gonadotropin-Releasing Hormone Antagonist J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 91 - 97. [Abstract] [Full Text] [PDF]

				M. Zitzmann, M. Depenbusch, J. Gromoll, and E. Nieschlag X-Chromosome Inactivation Patterns and Androgen Receptor Functionality Influence Phenotype and Social Characteristics as Well as Pharmacogenetics of Testosterone Therapy in Klinefelter Patients J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6208 - 6217. [Abstract] [Full Text] [PDF]

				Y. Ruhayel, K. Lundin, Y. Giwercman, C. Hallden, M. Willen, and A. Giwercman Androgen receptor gene GGN and CAG polymorphisms among severely oligozoospermic and azoospermic Swedish men Hum. Reprod., September 1, 2004; 19(9): 2076 - 2083. [Abstract] [Full Text] [PDF]

				A. Ferlin, L. Bartoloni, G. Rizzo, A. Roverato, A. Garolla, and C. Foresta Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility Mol. Hum. Reprod., June 1, 2004; 10(6): 417 - 421. [Abstract] [Full Text] [PDF]

				J. Eberhard, O. Stahl, Y. Giwercman, M. Cwikiel, E. Cavallin-Stahl, K.B. Lundin, P. Flodgren, and A. Giwercman Impact of therapy and androgen receptor polymorphism on sperm concentration in men treated for testicular germ cell cancer: a longitudinal study Hum. Reprod., June 1, 2004; 19(6): 1418 - 1425. [Abstract] [Full Text] [PDF]

				D. Milatiner, D. Halle, M. Huerta, E. J. Margalioth, Y. Cohen, A. Ben-Chetrit, M. Gal, T. Mimoni, and T. Eldar-Geva Associations between androgen receptor CAG repeat length and sperm morphology Hum. Reprod., June 1, 2004; 19(6): 1426 - 1430. [Abstract] [Full Text] [PDF]

				P. Y. Liu, A. K. Death, and D. J. Handelsman Androgens and Cardiovascular Disease Endocr. Rev., June 1, 2003; 24(3): 313 - 340. [Abstract] [Full Text] [PDF]

				M. Zitzmann, M. Depenbusch, J. Gromoll, and E. Nieschlag Prostate Volume and Growth in Testosterone-Substituted Hypogonadal Men Are Dependent on the CAG Repeat Polymorphism of the Androgen Receptor Gene: A Longitudinal Pharmacogenetic Study J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2049 - 2054. [Abstract] [Full Text] [PDF]

				L. Mengual, J. Oriola, C. Ascaso, J. L. Ballesca, and R. Oliva An Increased CAG Repeat Length in the Androgen Receptor Gene in Azoospermic ICSI Candidates J Androl, March 1, 2003; 24(2): 279 - 284. [Abstract] [Full Text] [PDF]

				S. Dejager, H. Bry-Gauillard, E. Bruckert, B. Eymard, F. Salachas, E. LeGuern, S. Tardieu, R. Chadarevian, P. Giral, and G. Turpin A Comprehensive Endocrine Description of Kennedy's Disease Revealing Androgen Insensitivity Linked to CAG Repeat Length J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3893 - 3901. [Abstract] [Full Text] [PDF]