星形胶质细胞衍生的外泌体调节精子miR-34c水平,介导父亲慢性社会不稳定压力的跨代效应。

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-01-27 DOI:10.1080/15592294.2025.2457176
Alexandre Champroux, Mitra Sadat-Shirazi, Xuan Chen, Jonathan Hacker, Yongjie Yang, Larry A Feig
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引用次数: 0

摘要

长期应激的雄性小鼠的影响可以通过其精子miRNA含量的应激特异性变化而代代相传,从而在其后代中诱导应激特异性表型。然而,每种应激模式如何改变不同的精子mirna组的水平尚不清楚。我们之前的研究表明,雄性小鼠暴露于慢性社会不稳定(CSI)压力下会导致其雌性后代的焦虑升高和社交能力下降,特别是在多代中,因为它降低了应激雄性及其非应激雄性后代精子中的miR-34c水平。在这里,我们描述了携带miR-34c的星形胶质细胞衍生外泌体(A-Exos)介导CSI应激对精子的跨代影响的证据。我们发现,CSI应激降低了男性前额皮质和杏仁核中A-Exos携带的miR-34c以及血液中的miR-34c。重要的是,在它们的F1雄性后代的这些组织中,miR-34c A-Exos水平也降低了,尽管没有暴露在压力下,但精子miR-34c水平降低,并将相同的压力相关性状传递给它们的雄性和雌性后代。此外,通过静脉注射含有miR-34c的A-Exos,恢复csi应激男性血液中A-Exos miR-34c的含量,恢复其精子中miR-34c的水平。这些发现揭示了a - exos在维持精子miR-34c水平中的意想不到的作用,该过程在被CSI应激抑制时介导了这种跨代表观遗传的例子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Astrocyte-derived exosomes regulate sperm miR-34c levels to mediate the transgenerational effects of paternal chronic social instability stress.

The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content, which induce stress-specific phenotypes in their offspring. However, how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not known. We showed previously that exposure of male mice to chronic social instability (CSI) stress results in elevated anxiety and reduced sociability specifically in their female offspring across multiple generations because it reduces miR-34c levels in sperm of stressed males and their unstressed male offspring. Here, we describe evidence that astrocyte-derived exosomes (A-Exos) carrying miR-34c mediate how CSI stress has this transgenerational effect on sperm. We found that CSI stress decreases miR-34c carried by A-Exos in the prefrontal cortex and amygdala, as well as in the blood of males. Importantly, miR-34c A-Exos levels are also reduced in these tissues in their F1 male offspring, who despite not being exposed to stress, exhibit reduced sperm miR-34c levels and transmit the same stress-associated traits to their male and female offspring. Furthermore, restoring A-Exos miR-34c content in the blood of CSI-stressed males by intravenous injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal an unexpected role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.

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来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
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