Paracrine and molecular regulation of the spermatogonial stem cell niche in zebrafish (Danio rerio) and the use of common carp (Cyprinus carpio) as a model to delay spermatogonial differentiation during puberty

Abstract

Spermatogonial stem cell (SSC) niche are specific regions of the testes which regulate stem cell properties, such as, self-renewal, differentiation, apoptosis, quiescence and pluripotency. The regulation of the SSC niche is essential to avoid accumulation of SSC (seminoma), when self-renewal is favored, or spermatogenesis depletion when differentiation is predominant over self-renewal. Characterization of SSC niche and its regulation have been drawn attention of several studies, including those with teleost fish, in particular with zebrafish. Zebrafish SSC niche is formed by Sertoli cells surrounding SSC, and adjacent interstitial cells, such as Leydig cells and blood vessels. Follicle-stimulating hormone (Fsh), and growth factors, as Amh (Anti-Müllerian hormone) and Igf3 (Insulin growth factor-like) have an important role on zebrafish SSC nice. While Amh inhibits spermatogonial differentiation and maintains SSC in their undifferentiated state, being down-regulated by Fsh, Igf3, induced by Fsh, promotes differentiation and spermatogonial proliferation towards meiosis. However, it remains unclear how Amh and Igf3 interact among each other, and the molecular changes induced by them on the SSC niche. This project aims to evaluate the interaction (direct or indirect) between Amh and Igf3, and analyze in particular the global gene profile induced by Amh, in order to determine potential candidates (mRNAs or microRNAs) involved in the inhibition of the SSC differentiation in zebrafish. And finally, increasing Amh expression through transient gene transfer, the project aims to delay spermatogonial differentiation during carp puberty. (AU)