Inverse correlation between sperm concentration and number of androgen receptor CAG repeats in normal men

Androgens are essential for the maintenance of normal spermatogenesis. Andr ogen action is mediated by the androgen receptor (AR), which in the testis is expressed by Leydig, peritubular, and Sertoli cells. The fact that sperm numbers range from 20 up to 300 million/mL in normal men without any indic ation of changed endocrine parameters led us to assume that genetic variabi lity of transduction of androgen signaling could be important. We therefore compared the variable number of CAG repeats in the AR with sperm concentra tions in men with normal ejaculate parameters (62 fathers and 69 volunteers participating in clinical trials). In multivariate analysis CAG repeat len gth did not differ between the volunteers (19.4 +/- 3.1) and the fathers (2 0.6 +/- 3.0), but was significantly correlated to sperm concentrations with a coefficient of -0.25. When compared with a group of infertile men with ( n = 14) or without (n = 30) a family history of infertility, no such correl ation was found. These results indicate that men with short CAG repeats hav e the highest sperm output within the normal fertile population. Polymorphi sms of the AR contribute to the efficiency of spermatogenesis in normal men , but do not play a predominant role in male infertility.