Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility?

• Published in: Journal of assisted reproduction and genetics Vol. 31; no. 6; pp. 689 - 697
• Main Authors: Giagulli, V. A., Carbone, M. D., De Pergola, G., Guastamacchia, E., Resta, F., Licchelli, B., Sabbà, C., Triggiani, V.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2014; Springer Nature B.V
• Subjects: Adult; Androgens; Chromosome Deletion; Chromosomes, Human, Y - genetics; Cryptorchidism; Endocrinology; Fertility; Genetics; Gynecology; Human Genetics; Humans; Infertility; Infertility, Male - genetics; Male; Males; Medicine; Medicine & Public Health; Metabolic disorders; Middle Aged; Oligospermia - genetics; Oligospermia - pathology; Outpatient care facilities; Plasma; Polymorphism; Receptors, Androgen - genetics; Reproductive Medicine; Sex Chromosome Aberrations; Sex Chromosome Disorders of Sex Development - genetics; Sex Chromosome Disorders of Sex Development - pathology; Sperm; Sperm Count; Sperm Motility; Spermatogenesis; Spermatogenesis - genetics; Testosterone; Trinucleotide Repeats - genetics; Y chromosomes; Italy; Y chromosome long arm microdeletions; Idiopathic male infertility; Sertoli cell; Inhibin B and testosterone; CAG repeat length polymorphism; Leydig cell
• ISSN: 1058-0468; 1573-7330; 1573-7330
• DOI: 10.1007/s10815-014-0221-4

Purpose This study examined whether the AR-CAG repeat length might affect clinical characteristics (testis volume) seminal parameters (sperm count and its mobility) along with hormonal serum profile [FSH, LH, Testosterone (T) and Inhibin B (InhB)] both in idiopathic male infertility (IM) and in infertility due to a previous condition of cryptorchidism (CryM) or to Y chromosome long arm microdeletions (YM). Design Observational study without intervention(s). Patients One hundred and ten IM patients [90 idiopathic olizoospermic males (IOM) and 20 idiopathic azoospermic males (IAM)], 19 CryM male and 10 YM patients were included. Sixty-one age-matched healthy men who had fathered within 3 years were involved representing the control group (FM). Results AR-CAG repeats stretch was significantly longer in IOM ( p  < 0.05), CryM ( p  < 0.05) and YM ( p  < 0.001) than FM. When the AR-CAG repeat tracts were subdivided in three subgroups according to the length of CAG repeats tract assessed in fertile subjects (the one with the middle (n 19–21) belonging to the 25 and 75 % inter-quartile, the ends belonging to the <25 % inter-quartile and >75 % inter-quartile, respectively), there was a statistically significant difference of distribution of AR-CAG tract length among fertile and different groups of infertile men ( p  = < 0.0005; chi-square test). Moreover, the subgroup of AR-CAG repeat stretch with 22–28 triplets was associated with lower levels of InhB both in idiopathic oligozoospermic (Scheffe, Bonferroni and Dunett tests p  = < 0.01) and azoospermic men (Scheffe, Bonferroni and Dunett test p  = < 0.05), while, when FM and men with idiopathic infertility were gathered in a single group, both the subgroup of AR- CAG tract with 15–18 repeats and the one with 22–28 repeats are associated with lower testis volume, reduced sperm count and serum InhB levels. Conclusions Our study showed that the outliers of AR-CAG repeat length seem to influence the function of AR, affecting testis volume and Sertoli cell function and consequently sperm production in both fertile and idiopathic infertile men.