Non-cell Autonomous Regionalization of Sertoli Valve Epithelia in the Terminal Segment of the Seminiferous Tubules of Mouse Testes

In mammalian testes, undifferentiated spermatogonia undergo meiotic differentiation in high retinoic acid (RA) signaling states, while their undifferentiated states are maintained by fibroblast growth factors (FGFs) and glial cell line-derived neurotrophic factor (GDNF), the major niche factors for spermatogonial stem/progenitor cells, in the basal compartment of the convoluted seminiferous tubules (STs). In the valve-like terminal end of the STs adjacent to the rete testis (RT), the Sertoli valve (SV) epithelia constitutively lack most spermatogenesis activity due in part to high GDNF expression, leading to the SV-specific enrichment of undifferentiated spermatogonia; however, the molecular and cellular characteristics of the SV epithelia are unclear. By performing a Sertoli cell ablation/replacement experiment using a mouse diphtheria toxin receptor-mediated system, we show here that the SV epithelia are non-cell autonomously specified, together with having high AKT phosphorylation, in the Sertoli cells located adjacent to the RT epithelia. RNA analyses revealed constitutively high expression of Cyp26a1, which encodes an RA-degrading enzyme, in the SV region, together with high expression of Fgf9 in the adjacent RT. Exogenous in vivo RA treatment induced meiotic differentiation of the spermatogonia located within the SV region, leading to disruption of the SV structure by the ectopic appearance of adluminal meiotic germ cells in some severely affected STs. We therefore propose that the regionalization and inactive spermatogenesis of SV epithelia are mediated in part by low RA signaling, together with high FGF9 signals in the terminal end of the STs. Overall design: SV fragments mRNA profiles from 7-week-old W/Wv mouse testes were generated using Illumina 2500.