Purpose: Androgens and a functioning androgen receptor are required for normal spermatogenesis. The androgen receptor gene (AR) has a repetitive DNA sequence in exon 1 that encodes a polyglutamine tract. Within the normal polymorphic range this (CAG)(n) tract length is inversely related to the transcriptional activity of the androgen receptor. In a prospective analysis we determined the association of AR (CAG)(n) tract length with testicular histology in infertile males.
Materials and methods: Blood DNA from 70 severely infertile patients without obstruction who were undergoing testicular biopsy was amplified by polymerase chain reaction targeting the AR (CAG)(n) tract. A total of 37, 15 and 18 men presented with the Sertoli-cell-only syndrome, maturation arrest and hypospermatogenesis, respectively. Blood DNA from 55 fertile men served as the control. Polymerase chain reaction amplified DNA was direct sequenced using a genetic analyzer.
Results: Median CAG repeat length was 22 (range 17 to 33) in infertile patients and 21 (range 8 to 27) in controls (p = 0.009), including 22 (range 17 to 30) in patients with the Sertoli-cell-only syndrome, 22 (range 18 to 28) in those with maturation arrest and 23 (19 to 33) in those with hypospermatogenesis. Statistical significance was noted for the hypospermatogenesis versus control groups (p = 0.039) but not for the groups with the Sertoli-cell-only syndrome or maturation arrest versus the control group (p = 0.054 and 0.591, respectively).
Conclusions: Infertile males with testicular failure, particularly those with hypospermatogenesis, are more likely to have a longer androgen receptor polyglutamine tract than controls. Polymorphisms of the AR (CAG)(n) tract may contribute to spermatogenesis efficiency through a subtle modulatory effect on androgen receptor function.