Sertoli cell‐derived exosomal MicroRNA‐486‐5p regulates differentiation of spermatogonial stem cell through PTEN in mice

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 different...

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Published in:Journal of cellular and molecular medicine 2021-04, Vol.25 (8), p.3950-3962
Main Authors: Li, Quan, Li, Hanhao, Liang, Jinlian, Mei, Jiaxin, Cao, Zhen, Zhang, Lei, Luo, Jiao, Tang, Yan, Huang, Rufei, Xia, Huan, Zhang, Qihao, Xiang, Qi, Yang, Yan, Huang, Yadong
Format: Article
Language:English
Subjects:
Animals
Antibodies
Cell differentiation
Cell interactions
Cell self-renewal
Cell signaling
differentiation
exosome
Exosomes
Fertility
Fibroblasts
Growth factors
Infertility
Microenvironments
MicroRNAs
miRNA
miR‐486‐5p
Molecular modelling
Original
Proteins
PTEN protein
Retinoic acid
Sertoli cells
Spermatogenesis
spermatogonial stem cells
Stem cells
Testes
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Summary: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.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.16347