CONICET | Buscador de Institutos y Recursos Humanos

The onset of spermatogenesis is androgen-dependant. Because germ cells do not express the androgen receptor (AR), Sertoli cells are believed to transduce testosterone (T) signals to them. This can only happen once AR expression in Sertoli cells begins around day 4. Expression of Aldh1a1, a retinoic acid (RA) synthesizing enzyme, is detectable by at least day 5 in Sertoli cells. RA induces expression of Stra8, which is associated with spermatogonial differentiation and meiotic onset. In the Aldh1a1-null mouse testis, Stra8 expression during the first wave of spermatogenesis is delayed. We hypothesise that androgens trigger the first wave of spermatogenesis by inducing the expression of ALDH1A1 in Sertoli cells of the pre-pubertal testis. TM4 cells were treated with T (10-8 M) or vehicle and Aldh1a1 expression was evaluated by qRT-PCR (ΔΔCt method, one sample t-test against 100% control, n=3 to 6). Aldh1a1 was upregulated by a 1 h (P=0.013), 2 h (P=0.009), 4 h (P=0.018) or 8 h (P=0.036) treatment and was expressed at four-fold baseline levels (P=0.031) after 24 h. Treatment with the antiandrogen Bicalutamide reversed this upregulation. Bioinformatic analysis showed two putative androgen response elements upstream of the transcription start site and two within intron 1 of the Aldh1a1 gene. Preliminary immunofluorescence results from pre-pubertal testis of RARE-lacZ reporter mice show co-localization of STRA8 and β-galactosidase (evidence for RA action) and weak expression of the AR in some Sertoli cell nuclei starting at 2 days. We conclude that androgens induce upregulation of Aldh1a1 acting through the AR and that Aldh1a1 upregulation might occur by both genomic and non-genomic mechanisms. Thus, testosterone may be important not just for the maintenance but also for the onset of spermatogenesis, acting via upregulation of ALDH1A1 in Sertoli cells.