O-GlcNAc participates in the meiosis of aging oocytes by mediating mitochondrial function.

IF 3.7 3区 生物学 Q1 DEVELOPMENTAL BIOLOGY
Reproduction Pub Date : 2024-11-14 Print Date: 2024-12-01 DOI:10.1530/REP-24-0138
Chuwei Li, Zhang Qian, Hong Zhang, Xie Ge, Li Chen, Mengqi Xue, Ting Tang, Zhaowanyue He, Lu Zheng, Chun Cao, Kemei Zhang, Rujun Ma, Bing Yao
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Abstract

In brief: O-GlcNAc plays an important role in many age-related diseases. This study shows that O-GlcNAc participates in oocyte aging and that reducing O-GlcNAc levels in aging oocytes improves oocyte quality.

Abstract: With an increase in the mean age at parturition worldwide, female reproductive aging has become a key health problem. Advanced maternal age is reflected by decreased oocyte quality; however, the molecular mechanisms of oocyte aging are uncharacterized. O-linked N-acetylglucosamine (O-GlcNAc), a dynamic posttranslational modification, plays a critical role in the development of many age-related diseases; yet, it remains unclear whether and how O-GlcNAc participates in oocyte aging. Here, we found that global O-GlcNAc was elevated in normal biological aging mice oocytes (9 months), which were characterized by meiotic maturation failure and impaired mitochondrial function. Specifically, O-GlcNAc targeted the mitochondrial fission protein dynamic-related protein 1 to mediate mitochondrial distribution in the process of aging. Using the O-GlcNAcase (OGA) pharmacological inhibitor Thiamet-G and Oga knockdown (Oga-KD) to mimic the age-related high O-GlcNAc in young oocytes from 6-8 week-old mice mimicked the phenotype of oocyte aging. Moreover, reducing O-GlcNAc levels in aging oocytes restored spindle organization to improve oocyte quality. Our results demonstrate that O-GlcNAc is a key regulator of meiotic maturation that participates in the progression of oocyte aging.

O-GlcNAc 通过介导线粒体功能参与衰老卵母细胞的减数分裂。
随着全球平均分娩年龄的增加,女性生殖衰老已成为一个关键的健康问题。高龄产妇的表现是卵母细胞质量下降;然而,卵母细胞衰老的分子机制尚未定性。O-连接的N-乙酰葡糖胺(O-GlcNAc)是一种动态的翻译后修饰,在许多与年龄有关的疾病的发展中起着关键作用,但目前仍不清楚O-GlcNAc是否以及如何参与卵母细胞的衰老。在这里,我们发现在正常生物衰老小鼠卵母细胞(32-34 周)中,全局 O-GlcNAc 升高,其特征是减数分裂成熟失败和线粒体功能受损。具体来说,O-GlcNAc 以线粒体裂变蛋白动态相关蛋白 1(DRP1)为靶标,介导衰老过程中的线粒体分布。使用O-GlcNA酶(OGA)药理抑制剂Thiamet-G和OGA基因敲除(OGA-KD)来模拟6-8周龄小鼠年轻卵母细胞中与年龄相关的高O-GlcNAc,模拟了卵母细胞衰老的表型。此外,降低衰老卵母细胞中的 O-GlcNAc 水平可恢复纺锤体组织,从而改善卵母细胞质量。我们的研究结果表明,O-GlcNAc 是减数分裂成熟的一个关键调节因子,它参与了卵母细胞衰老的进程。
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
Reproduction
Reproduction 生物-发育生物学
CiteScore
7.40
自引率
2.60%
发文量
199
审稿时长
4-8 weeks
期刊介绍: Reproduction is the official journal of the Society of Reproduction and Fertility (SRF). It was formed in 2001 when the Society merged its two journals, the Journal of Reproduction and Fertility and Reviews of Reproduction. Reproduction publishes original research articles and topical reviews on the subject of reproductive and developmental biology, and reproductive medicine. The journal will consider publication of high-quality meta-analyses; these should be submitted to the research papers category. The journal considers studies in humans and all animal species, and will publish clinical studies if they advance our understanding of the underlying causes and/or mechanisms of disease. Scientific excellence and broad interest to our readership are the most important criteria during the peer review process. The journal publishes articles that make a clear advance in the field, whether of mechanistic, descriptive or technical focus. Articles that substantiate new or controversial reports are welcomed if they are noteworthy and advance the field. Topics include, but are not limited to, reproductive immunology, reproductive toxicology, stem cells, environmental effects on reproductive potential and health (eg obesity), extracellular vesicles, fertility preservation and epigenetic effects on reproductive and developmental processes.
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