Contribution of Recent Transgenic Models and Transcriptional Profiling Studies to Our Understanding of the Mechanisms by which Androgens Control Spermatogenesis

Androgens play a key role in the control of spermatogenesis and interference with their intratesticular secretion and action is a critical element in many contraceptive strategies. Nonetheless, the cellular and molecular mechanisms by which androgens control germ cell development remain poorly understood. Recent transgenic models in which the androgen receptor (AR) is selectively ablated in Sertoli cells show unambiguously that the Sertoli cell is the main target for androgen action in the control of spermatogenesis. A number of additional mouse models have been developed mimicking human diseases in which mutations of the AR cause disturbed fertility without affecting male development. Transcriptional profiling studies in mice with Sertoli cell-selective AR ablation and in some other experimental paradigms have tried to identify androgen-regulated genes relevant to the control of spermatogenesis. The overlap in genes identified in different studies is poor but this may be due mainly to dissimilarities in experimental setup. In all studies, relatively large numbers of genes rather than a few key genes seem to be affected by androgen action. Genes related to tubular restructuring, cell junction dynamics, cytoskeleton, solute transportation and vitamin A metabolism are prominently present. Although further work is obviously needed, it may be anticipated that these studies will result in the identification of subsets of genes that can be used as diagnostic tools as well as in the identification of targets for the development of novel contraceptives. Keywords: Testis, androgen receptor, cell-selective knockout, microarray, Sertoli cell