期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 8, 页码 3950-3962出版社
WILEY
DOI: 10.1111/jcmm.16347
关键词
differentiation; exosome; miR‐ 486‐ 5p; Sertoli cells; spermatogonial stem cells
资金
- China Postdoctoral Science Foundation [2017M622914, 2019M663100]
- National Natural Science Foundation of China [31801235, 81871150, 81901470, 82071634]
- Natural Science Foundation of Guangdong Province [2018A030313473]
- Medical Scientific Research Foundation of Guangdong Province of China [B2020139]
- Science and Technology Plan Project of Guangzhou [201508020001, 2016A020214013, 201704YG066, 201803010044, 2020A1515011203]
The study reveals the role of miR-486-5p in mediating communication between Sertoli cells and SSCs through exosomes, promoting the differentiation of SSCs. This provides new insights into the molecular mechanisms regulating SSC differentiation.
Self-renewal and differentiation of spermatogonial stem cell (SSC) are critical for male fertility and reproduction, both of which are highly regulated by testicular microenvironment. Exosomal miRNAs have emerged as new components in intercellular communication. However, their roles in the differentiation of SSC remain unclear. Here, we observed miR-486-5p enriched in Sertoli cell and Sertoli cell-derived exosomes. The exosomes mediate the transfer of miR-486-5p from Sertoli cells to SSCs. Exosomes release miR-486-5p, thus up-regulate expression of Stra8 (stimulated by retinoic acid 8) and promote differentiation of SSC. And PTEN was identified as a target of miR-486-5p. Overexpression of miR-486-5p in SSCs down-regulates PTEN expression, which up-regulates the expression of STRA8 and SYCP3, promotes SSCs differentiation. In addition, blocking the exosome-mediated transfer of miR-486-5p inhibits differentiation of SSC. Our findings demonstrate that miR-486-5p acts as a communication molecule between Sertoli cells and SSCs in modulating differentiation of SSCs. This provides a new insight on molecular mechanisms that regulates SSC differentiation and a basis for the diagnosis, treatment, and prevention of male infertility.
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