Mutations of the Human Androgen Receptor Gene in Men Infertile from Testicular Causes

Kim, Soo Woong; Yun, Jong Min; Kang, Jeongyoon; Kim, Ki Dong; Paick, Jae Seung

Abstract

PURPOSE: Many men with a normal phenotype but decreased or absent production may have abnormalities of the androgen receptor (AR). Here, we investigated men with severe oligospermia and azoospermia to ascertain wether mutations of the AR gene are associated with male infertility having testicular causes.
PATIENTS AND METHODS
A total of 43 infertile men with a normal phenotype and severe oligospermia or azoospermia and three normally fertile men entered this study. Included was one man with known incomplete androgen insensitivity syndrome (AIS). Deoxyribonucleic acid was isolated from peripheral blood samples of the subjects, and polymerase chain reaction (PCR) was carried out using sets of primers designed to amplify sequences of eight exons of the AR gene. For convenience and repidity of analyses, the multiplex PCR method was employed.
RESULTS
PCR resulted in amplification of all eight exons. In all samples, amplified products were shown to be appropriate-sized bands on agarose gels. No gross abnormalities were found in most of the infertile patients. However, an increased number of CAG repeat in exon 1 of the AR gene and point mutations (T to C, nt 3897; A to T, nt 3903) in exon 7 were found in the AIS subject.
CONCLUSIONS
Our results showed no gross deletions of the AR gene in most infertile subjects. However, point mutations may have been overlooked by the techniques used, as demonstrated in the AIS subject. Further study will be required to clarify expression and localization of AR I the testis and consequently to understand the precise roles of the AR in regulating the normal spermatogenesis.