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Sertoli 细胞衍生的外泌体 MicroRNA-486-5p 通过 PTEN 调控小鼠精原干细胞的分化。

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

机构信息

Department of Cell Biology & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, China.

Department of Pharmacology, Jinan University, Guangzhou, China.

出版信息

J Cell Mol Med. 2021 Apr;25(8):3950-3962. doi: 10.1111/jcmm.16347. Epub 2021 Feb 19.

DOI:10.1111/jcmm.16347
PMID:33608983
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8051706/
Abstract

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.

摘要

精原干细胞（SSC）的自我更新和分化对于雄性生育和繁殖至关重要，而这两者都受到睾丸微环境的高度调节。外泌体 miRNAs 已成为细胞间通讯的新成分。然而，它们在 SSC 分化中的作用尚不清楚。在这里，我们观察到 miR-486-5p 在支持细胞和支持细胞衍生的外泌体中富集。外泌体介导 miR-486-5p 从支持细胞到 SSC 的转移。外泌体释放 miR-486-5p，从而上调 Stra8（维甲酸 8 刺激）的表达并促进 SSC 的分化。并且鉴定出 PTEN 是 miR-486-5p 的靶标。SSC 中转录上调 miR-486-5p 下调 PTEN 表达，上调 STRA8 和 SYCP3 的表达，促进 SSCs 分化。此外，阻断 miR-486-5p 的外泌体介导转移抑制 SSC 的分化。我们的研究结果表明，miR-486-5p 在调节 SSC 分化中作为支持细胞和 SSC 之间的通讯分子发挥作用。这为调控 SSC 分化的分子机制提供了新的见解，并为男性不育的诊断、治疗和预防提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/6fdcd7852865/JCMM-25-3950-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/ce0ea9646d30/JCMM-25-3950-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/58ca7fd06c96/JCMM-25-3950-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/ca4837411ef8/JCMM-25-3950-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/0bd274230874/JCMM-25-3950-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/41bf8f43727b/JCMM-25-3950-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/828ca12f213f/JCMM-25-3950-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/6fdcd7852865/JCMM-25-3950-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/ce0ea9646d30/JCMM-25-3950-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/58ca7fd06c96/JCMM-25-3950-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/ca4837411ef8/JCMM-25-3950-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/0bd274230874/JCMM-25-3950-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/41bf8f43727b/JCMM-25-3950-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/828ca12f213f/JCMM-25-3950-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bab9/8051706/6fdcd7852865/JCMM-25-3950-g005.jpg

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引用本文的文献

[1]
Knowledge mapping of exosomes in ischemic stroke: a bibliometric analysis.

Front Neurol. 2025-7-23

[2]
The effect of Sertoli cell exosomes on spermatogonia stem cells differentiation.

Bioimpacts. 2025-7-1

[3]
Extracellular vesicles in reproductive biology and disorders: a comprehensive review.

Front Endocrinol (Lausanne). 2025-6-4

[4]
Engineered extracellular vesicles: a breakthrough approach to overcoming sperm cryopreservation challenges.

Reprod Biol Endocrinol. 2025-5-21

[5]
Extracellular Vesicles in the Aging Male Reproductive System: Progresses and Perspectives.

Adv Exp Med Biol. 2025

[6]
The Biology and Regulation of Spermatogonial Stem Cells in the Niche.

Adv Exp Med Biol. 2025

[7]
Zinc finger DHHC-type palmitoyltransferase 13-mediated S-palmitoylation of GNA13 from Sertoli cell-derived extracellular vesicles inhibits autophagy in spermatogonial stem cells.

Cell Commun Signal. 2025-4-9

[8]
The role of Sertoli cell-derived miR-143-3p in male fertility declines with age.

Mol Ther Nucleic Acids. 2024-10-28

[9]
From Germ Cells to Implantation: The Role of Extracellular Vesicles.

J Dev Biol. 2024-8-23

[10]
Microenvironment of spermatogonial stem cells: a key factor in the regulation of spermatogenesis.

Stem Cell Res Ther. 2024-9-11

本文引用的文献

[1]
Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2.

Front Bioeng Biotechnol. 2020-4-8

[2]
Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing.

Cells. 2020-1-14

[3]
MiR-486-5p inhibits the proliferation of leukemia cells and induces apoptosis through targeting FOXO1.

Mol Cell Probes. 2019-2-5

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Role of miR-486-5p in regulating renal cell carcinoma cell proliferation and apoptosis via TGF-β-activated kinase 1.

J Cell Biochem. 2018-12-9

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Regulation and modulation of PTEN activity.

Mol Biol Rep. 2018-12

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miR-486-5p inhibits cell proliferation and invasion through repressing GAB2 in non-small cell lung cancer.

Oncol Lett. 2018-9

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Cancer Med. 2018-8-2

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MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity.

Biomaterials. 2017-11-21

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Fibroblast-derived exosomes promote epithelial cell proliferation through TGF-β2 signalling pathway in severe asthma.

Allergy. 2017-7-20

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BMP4 Cooperates with Retinoic Acid to Induce the Expression of Differentiation Markers in Cultured Mouse Spermatogonia.

Stem Cells Int. 2016

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