Retinoic acid and androgens interact to regulate spermatogenesis in a non-mammalian vertebrate lackingstra8

In mammals, retinoic acid (RA) signaling is critical for spermatogonial differentiation and for entering meiosis, the latter depending on RA-induced Stra8 gene expression. Many fish species, including zebrafish, do not contain a stra8 gene, but RA signaling nevertheless is important for sperm production. However, it is not known which stages of spermatogenesis respond to RA. Here, we show in zebrafish that RA promotes spermatogonial differentiation and reduces the apoptotic loss of spermatids, but is not required for meiosis. Some of the RA effects are mediated by other genes, in particular rec8a . Surprisingly, androgens can partially compensate for the loss of RA signaling, and we identify a link between the endocrine system and RA signaling: follicle-stimulating hormone (Fsh) stimulates testicular RA production. While RA signaling is relevant at the basis of the vertebrates, it also targets processes and mechanisms that are different from those known in mammals so far.