Exosome-derived Small RNAs in mouse Sertoli cells inhibit spermatogonial apoptosis

Abstract

Spermatogenesis is a highly complicated biological process that occurs in the epithelium of the seminiferous tubules. It is regulated by a complex network of endocrine and paracrine factors. Sertoli cells (SCs) play a key role in spermatogenesis due to their production of trophic, differentiation, and immune-modulating factors. However, many of the molecular pathways of SC action remain controversial and unclear. Recently, many studies have focused on exosomes as an important mechanism of intercellular communication. We found that the exosomes derived from mouse SCs inhibited the apoptosis of primary spermatogonia. A total of 1016 miRNAs in SCs and 556 miRNAs in exosomes were detected using miRNA high-throughput sequencing. A total of 294 miRNAs were differentially expressed between SCs and exosomes. Furthermore, 19 tsRNA families appeared in SCs, while 6 tsRNA families appeared in exosomes. A total of 57 and 1 miRNAs (RPM >4) and 14 and 1 tsRNAs were exclusively expressed in SCs and exosomes, respectively. MiR-10b is one of the top ten exosomes with a relatively large enrichment of miRNA. Overexpression of miR-10b downregulates the expression of the target KLF4 to reduce spermatogonial apoptosis in primary spermatogonia or the C18-4 cell line.