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出生后早期应激对支持细胞的长期影响。

Long-term effects of early postnatal stress on Sertoli cells.

作者信息

Thumfart Kristina M, Lazzeri Samuel, Manuella Francesca, Mansuy Isabelle M

机构信息

Laboratory of Neuroepigenetics, Neuroscience Center Zürich, Brain Research Institute, Medical Faculty of the University Zürich, and Institute of Neuroscience of the Department of Health Science and Technology, ETH Zürich, Zurich, Switzerland.

IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.

出版信息

Front Genet. 2022 Oct 24;13:1024805. doi: 10.3389/fgene.2022.1024805. eCollection 2022.

Abstract

Sertoli cells are somatic cells in testis essential for spermatogenesis, that support the development, maturation, and differentiation of germ cells. Sertoli cells are metabolically highly active and physiologically regulated by external signals, particularly factors in the blood stream. In disease conditions, circulating pathological signals may affect Sertoli cells and consequentially, alter germ cells and fertility. While the effects of stress on reproductive cells have been well studied, how Sertoli cells respond to stress remains poorly characterized. We used a mouse model of early postnatal stress to assess the effects of stress on Sertoli cells. We developed an improved strategy based on intracellular stainings and obtained enriched preparations of Sertoli cells from exposed males. We show that adult Sertoli cells have impaired electron transport chain (ETC) pathways and that several components of ETC complexes particularly complex I, III, and IV are persistently affected. We identify serum as potential mediator of the effects of stress on Sertoli cells by showing that it can recapitulate ETC alterations in primary cells. These results highlight Sertoli cells as cellular targets of stress in early life that can keep a trace of exposure until adulthood.

摘要

支持细胞是睾丸中的体细胞,对精子发生至关重要,它支持生殖细胞的发育、成熟和分化。支持细胞代谢高度活跃,在生理上受外部信号调节,尤其是血流中的因子。在疾病状态下,循环中的病理信号可能影响支持细胞,进而改变生殖细胞和生育能力。虽然应激对生殖细胞的影响已得到充分研究,但支持细胞如何对应激作出反应仍知之甚少。我们使用产后早期应激的小鼠模型来评估应激对支持细胞的影响。我们基于细胞内染色开发了一种改进策略,并从暴露的雄性小鼠中获得了富集的支持细胞制剂。我们发现成年支持细胞的电子传递链(ETC)途径受损,并且ETC复合物的几个组分,特别是复合物I、III和IV持续受到影响。通过表明血清可在原代细胞中重现ETC改变,我们确定血清是应激对支持细胞产生影响的潜在介质。这些结果突出了支持细胞作为生命早期应激的细胞靶点,它可以保留应激暴露的痕迹直至成年。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/480b/9638847/4af9052a1a6c/fgene-13-1024805-g001.jpg

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