Evaluation of CAG repeat length of androgen receptor expressing cells in human testes showing different pictures of spermatogenic impairment

Abstract

The androgen receptor (AR) is a ligand-activated transcriptional factor with crucial importance for spermatogenesis. Its transactivation domain consists of a polymorphic sequence of 9-36 cytosin-adenin-guanin (CAG) repeats. Within the physiological range an increased CAG repeat length is assumed to correlate with the reduced androgen sensitivity resulting in impaired spermatogenesis. In 33 testes of 32 patients showing different histological pictures ranging from normal spermatogenesis, hypospermatogenesis to severe spermatogenetic impairment such as maturation arrest, Sertoli cell only Syndrome (SCO) and mixed atrophy, CAG repeat length was assessed in lymphocyte DNA, DNA/mRNA from testis homogenate and in mRNA of AR expressing Sertoli cells within the seminiferous tubules, and interstitial Leydig cells collected by the laser-assisted cell picking. The latter examination was performed to detect a possible somatic mosaicism of CAG repeat length in different testicular cell populations. CAG repeat lengths varied from 12 to 27 repeats, i.e., within the physiological range. We found deviating CAG repeat numbers in different fractions of AR expressing Sertoli and Leydig cells indicating tissue heterogeneity. We did not find a correlation of CAG repeat length to testicular histology or AR expression, and testosterone or luteinizing hormone levels even in biopsies showing mixed atrophy. Additionally, we evaluated the expression pattern of the AR-dependent gene androgen binding protein (ABP), and did not find a correlation to CAG repeat, but a significant reduction of ABP mRNA related to severe spermatogenic impairment in the monomorphic histologies. These data suggest other factors than CAG repeat to be responsible for severe spermatogenic impairment including mixed atrophy.