Is ALDH1A1 the link between androgens and spermatogenic onset?

EDELSZTEIN, NADIA Y.; REY, RODOLFO A.; SCHTEINGART, HELENA F.; FENG, CHUN-WEI; BOWLES, JOSEPHINE

Kingscliff, NSW 2487

Conferencia; Reproduction Down Under 2017; 2017

School of BioSciences, The University of Melbourne, Australia

It is known that 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 take place once AR expression in Sertoli cells begins around P4 or P5, as they remain until that time in a physiologically androgen-insensitive state. Expression of Aldh1a1, a weak catalyst of the final irreversible step in the production of retinoic acid (RA), is upregulated at P5 in Sertoli cells. It is well accepted that RA induces expression of Stra8 which, in the male, is associated with both spermatogonial differentiation and the initiation of meiosis. In the Aldh1a1-null mouse testis, onset of Stra8 expression during the first wave of spermatogenesis is delayed. Based on these observations we sought to elucidate whether there is a link between androgens and ALDH1A1 that is relevant to spermatogenic onset. We hypothesised that T triggers spermatogenesis by inducing the expression of ALDH1A1 in Sertoli cells of the pre-pubertal testis. We find that physiologically-relevant levels of T and DHT rapidly induce Aldh1a1 expression in the peri-pubertal mouse Sertoli cell line, TM4. Time-course analysis suggests that this might occur by both genomic and non-genomic mechanisms. We are now testing this mechanism in ex vivo cultures. We also aim to correlate presence of RA (RARE-lacZ reporter mice) with expression of ALDH1A1 and AR in Sertoli cells and STRA8 in germ cells of the pre-pubertal mouse testis.