FOXO4-DRI improves spermatogenesis in aged mice through reducing senescence-associated secretory phenotype secretion from Leydig cells

IF 3.9

Experimental gerontology Pub Date : 2024-07-19 DOI:10.1016/j.exger.2024.112522

Yanqing Li , Chi Zhang , Haicheng Cheng , LinYan Lv , Xinning Zhu , Menghui Ma , Zhenhan Xu , Junxian He , Yun Xie , Xing Yang , Xiaoyan Liang , Chunhua Deng , Guihua Liu

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引用次数: 0

Abstract

Male ageing is always accompanied by decreased fertility. The forkhead O (FOXO) transcription factor FOXO4 is reported to be highly expressed in senescent cells. Upon activation, it binds p53 in the nucleus, preventing senescent cell apoptosis and maintaining senescent cells in situ. Leydig cells play key roles in assisting spermatogenesis. Leydig cell senescence leads to deterioration of the microenvironment of the testes and impairs spermatogenesis. In this study, we observed that FOXO4-DRI, a specific FOXO4- p53 binding blocker, induced apoptosis in senescent Leydig cells, reduced the secretion of certain Senescence-Associated Secretory Phenotype and improved the proliferation of cocultured GC-1 SPG cells. In naturally aged mice, FOXO4-DRI-treated aged mice exhibited increased sperm quality and improved spermatogenesis.

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FOXO4-DRI 可通过减少髓质细胞与衰老相关的分泌表型分泌，改善老年小鼠的精子发生。

男性衰老总是伴随着生育能力的下降。据报道，叉头 O（FOXO）转录因子 FOXO4 在衰老细胞中高度表达。激活后，它与细胞核中的 p53 结合，阻止衰老细胞凋亡，并在原位维持衰老细胞。精原细胞在协助精子发生方面发挥着关键作用。髓质细胞衰老会导致睾丸微环境恶化，影响精子发生。在这项研究中，我们观察到特异性 FOXO4- p53 结合阻断剂 FOXO4-DRI 可诱导衰老的 Leydig 细胞凋亡，减少某些衰老相关分泌表型的分泌，并改善共培养 GC-1 SPG 细胞的增殖。在自然衰老的小鼠中，经 FOXO4-DRI 处理的衰老小鼠表现出精子质量提高和精子生成改善。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental gerontology Ageing, Biochemistry, Geriatrics and Gerontology

CiteScore

6.70

自引率

0.00%

发文量

审稿时长

66 days