Could Androgen Receptor Gene CAG Tract Polymorphism Affect Spermatogenesis in Men with Idiopathic Infertility?

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2014 Apr 3

PMID 24691874

Citations 6

Authors

V A Giagulli

M D Carbone

G De Pergola

E Guastamacchia

F Resta

B Licchelli

C Sabba

V Triggiani

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Association study of novel single nucleotide polymorphisms of androgen receptor and estrogen receptor-α genes with male infertility in Northwest of Iran: A case-control study.

Ghadirkhomi E, Angaji S, Khosravi M, Reza Mashayekhi M Int J Reprod Biomed. 2022; 20(6):501-510.

PMID: 35958962 PMC: 9358236. DOI: 10.18502/ijrm.v20i6.11446.

Androgen receptor ()-CAG trinucleotide repeat length and idiopathic male infertility: a case-control trial and a meta-analysis.

Mobasseri N, Babaei F, Karimian M, Nikzad H EXCLI J. 2019; 17:1167-1179.

PMID: 30713477 PMC: 6341423. DOI: 10.17179/excli2018-1744.

The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis.

Wu Q, Zhang J, Zhu P, Jiang W, Liu S, Ni M BMC Med Genet. 2017; 18(1):81.

PMID: 28764642 PMC: 5540502. DOI: 10.1186/s12881-017-0441-4.

Androgen receptor gene CAG and GGN repeat lengths as predictors of recovery of spermatogenesis following testicular germ cell cancer treatment.

Bogefors K, Lundberg Giwercman Y, Eberhard J, Stahl O, Cavallin-Stahl E, Cohn-Cedermark G Asian J Androl. 2016; 19(5):538-542.

PMID: 27873769 PMC: 5566846. DOI: 10.4103/1008-682X.191126.

Diagnosis and treatment of infertility-related male hormonal dysfunction.

Kathrins M, Niederberger C Nat Rev Urol. 2016; 13(6):309-23.

PMID: 27091665 DOI: 10.1038/nrurol.2016.62.

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