GENE EXPRESSION ALTERATIONS IN ADULT UTP14b (jsd) MICE BY CONDITIONAL KNOCKOUT OF ANDROGEN RECEPTOR IN SERTOLI CELLS

Spermatogenesis is dependent primarily on testosterone action on the Sertoli cells. Although the identification of testosterone-regulated target genes in Sertoli cells has been approached using microarray analysis to compare gene expression in mice with androgen receptor (AR) elimination in the Sertoli cells (SCARKO) and wild type mice, the analysis has been complicated by alteration of germ cell composition of the testis when pubertal or adult mice were used and differences in Sertoli-cell gene expression from those in adult when prepubertal mice were used. Since the testicular cell components of adult jsd (Utp14bjsd ,juvenile spermatogonial depletion) mice and SCARKO-jsd mice are essentially identical, consisting of only type A spermatogonia and somatic cells, comparisons of gene expression profiles between jsd and SCARKO-jsd testes would identify AR regulated genes in adult Sertoli cells, with minimum effects of cell number changes. Microarray analysis identified 161 genes as downregulated and 202 genes as upregulated in the SCARKO-jsd mice compared to jsd mice. Some of the genes identified in the previous studies, including Rhox5, Drd4, and Fhod3, were also AR-regulated in the jsd testes but others, such as proteases and components of junctional complexes, were not androgen regulated in our model. Surprisingly, a set of germ-cell-specific genes preferentially expressed in differentiated spermatogonia and meiotic cells, including Meig1, Sycp3, and Ddx4, were all upregulated about 2-fold in SCARKO-jsd testes, demonstrating that, although there was no significant differentiation to spermatocytes in SCARKO-jsd mice, AR-regulated genes in Sertoli cells are involved in the regulation of spermatogonial differentiation. Further gene ontogeny analysis revealed possible sets of genes whose expression changes may be involved in the disruption of Sertoli cell organization in SCARKO-jsd testes. Comparisons of gene expression profiles between the testis of jsd mice (n=3) and SCARKO-jsd mice (n=3).