Melatonin mitigates ovarian aging through regulation of the YTHDF2/m6A/UBE3C axis.

IF 3.3 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Wenjuan Xia, Xin Wang, Jincheng Li, Ming Zhang, Jiafeng Lu, Hong Li, Quanze He, Qingxia Meng, Boxian Huang
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引用次数: 0

Abstract

Ovarian aging is a natural process characterized by a decline in both the quantity and quality of oocytes, which subsequently leads to diminished fertility, particularly in women over the age of 35. Given the societal trend toward postponing childbirth, it is imperative to understand the molecular mechanisms that underpin ovarian aging to address infertility issues. Melatonin (MT) is recognized for its therapeutic potential in mitigating ovarian aging; however, the specific epigenetic mechanisms involved, particularly concerning m6A methylation, remain inadequately defined. Our investigation demonstrates that MT mitigates ovarian aging in murine models, significantly decreasing m6A methylation levels. In vitro analyses of ovarian granulosa (KGN) cells reveals a marked increase in YTHDF2 expression, with differentially methylated genes being notably enriched in the polyubiquitination pathway. Further examination shows that YTHDF2 enhances the expression of the E3 ligase UBE3C by modulating the m6A methylation of UBE3C mRNA, thereby reducing the expression of the P53 senescence factor and alleviating the effects of ovarian aging.

.

褪黑素通过调节YTHDF2/m6A/UBE3C轴来减缓卵巢衰老。
卵巢衰老是一个自然过程,其特征是卵母细胞的数量和质量下降,从而导致生育能力下降,尤其是35岁以上的女性。鉴于推迟生育的社会趋势,了解卵巢老化的分子机制以解决不孕问题是势在必行的。褪黑素(MT)是公认的治疗潜力,减轻卵巢老化;然而,所涉及的具体表观遗传机制,特别是与m6A甲基化有关的机制,仍然没有得到充分的定义。我们的研究表明,在小鼠模型中,MT可以减缓卵巢衰老,显著降低m6A甲基化水平。卵巢颗粒(KGN)细胞的体外分析显示YTHDF2表达显著增加,差异甲基化基因在多泛素化途径中显著富集。进一步研究发现,YTHDF2通过调节UBE3C mRNA的m6A甲基化,增强E3连接酶UBE3C的表达,从而降低P53衰老因子的表达,缓解卵巢衰老的影响。
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
Acta biochimica et biophysica Sinica
Acta biochimica et biophysica Sinica 生物-生化与分子生物学
CiteScore
5.00
自引率
5.40%
发文量
170
审稿时长
3 months
期刊介绍: Acta Biochimica et Biophysica Sinica (ABBS) is an internationally peer-reviewed journal sponsored by the Shanghai Institute of Biochemistry and Cell Biology (CAS). ABBS aims to publish original research articles and review articles in diverse fields of biochemical research including Protein Science, Nucleic Acids, Molecular Biology, Cell Biology, Biophysics, Immunology, and Signal Transduction, etc.
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