Extracellular-vesicle-mediated transfer of let-7b/7c promotes the proliferation of transition-state spermatogonia in neonatal mouse testis

The self-renewal and differentiation of spermatogonial stem cells (SSCs) play essential roles in spermatogenesis. Extracellular vesicle (EV) is a universal strategy for intercellular communications in stem cell niches. However, the involvement of EVs in regulating SSCs remains largely unknown. This study revealed that testis EVs from postnatal day 7 (PND7) neonatal mouse testis guided spermatogonia into a transit-amplifying state with increased proliferation while retaining their differentiation potential. We profiled the repertoires of proteins and small RNAs by proteomic and small RNA transcriptomic analyses, respectively. We further showed that the EVs secreted by undifferentiated spermatogonia and the Sertoli cell lines, but not from more differentiated germ cell lines, conveyed let-7b/7c microRNA (miRNA) cargoes to spermatogonia, which mediated the effect of EVs on spermatogonial transit amplification. Together, this study has deciphered crucial let-7b/7c cargoes of EV-mediated communication within the spermatogonial niche, providing a new insight into the regulation of SSCs and spermatogenesis.