Sertoli cell-derived exosome-mediated transfer of miR-145-5p inhibits Leydig cell steroidogenesis by targeting steroidogenic factor 1

• Published in: The FASEB journal Vol. 35; no. 6; p. e21660
• Main Authors: Liang, Jinlian, Li, Hanhao, Mei, Jiaxin, Cao, Zhen, Tang, Yan, Huang, Rufei, Xia, Huan, Zhang, Qihao, Xiang, Qi, Yang, Yan, Huang, Yadong
• Format: Journal Article
• Language: English
• Published: United States 01.06.2021
• Subjects: Animals; Exosomes - genetics; Exosomes - metabolism; Leydig Cells - metabolism; Leydig Cells - pathology; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; Sertoli Cells - metabolism; Sertoli Cells - pathology; Steroidogenic Factor 1 - antagonists & inhibitors; Steroidogenic Factor 1 - genetics; Steroidogenic Factor 1 - metabolism; Steroids - biosynthesis; Testis - metabolism; Testis - pathology; Sertoli cell; testosterone; exosome; Leydig cell; miR-145-5p
• ISSN: 1530-6860
• DOI: 10.1096/fj.202002589RRRR

In the mammalian testis, two distinct populations of Sertoli cells (SCs), the immature SCs (ISCs) and adult SCs (ASCs), play significant roles in regulating the development and function of Leydig cells. However, the effect of different SC types on the function of Leydig cells is poorly understood. Here, our study showed that miR-145-5p expression was significantly different in SCs at different stages, with the highest expression observed in ISCs. Exosomes mediate the transfer of miR-145-5p from ISCs to Leydig cells. Overexpression of miR-145-5p in Leydig cells significantly downregulated steroidogenic gene expression and inhibited testosterone synthesis. Additionally, miR-145-5p functioned by directly targeted steroidogenic factor-1 (Sf-1) and downregulated the expression of SF-1, which further downregulated the expression of steroidogenic genes, induced accumulation of lipid droplets, and eventually suppressed testosterone production. These findings demonstrate that SC-derived miR-145-5p plays a significant role in regulating the functions of Leydig cells and may therefore serve as a diagnostic biomarker for male hypogonadism developmental abnormalities during puberty.