GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells.

IF 3.7 3区 生物学 Q1 DEVELOPMENTAL BIOLOGY Reproduction Pub Date : 2024-06-21 Print Date: 2024-08-01 DOI:10.1530/REP-24-0015
Canxin Wen, Linlin Jiang, Ping Pan, Jia Huang, Yanxin Xie, Songbang Ou, Yu Li
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Abstract

In brief: Ovarian aging results in reactive oxygen species accumulation and mitochondrial deterioration. During the aging process, GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells.

Abstract: Ovarian aging critically influences reproductive potential, with a marked decrease in oocyte quality and quantity and an increase in oxidative stress and mitochondrial dysfunction. This study elucidates the role of guanine-rich RNA sequence binding factor 1 (GRSF1) in the aging of ovarian granulosa cells (GCs). We observed a significant reduction in GRSF1 within GCs correlating with patient age, utilizing clinical samples from IVF patients. Using an siRNA-mediated knockdown technique, we established that diminished GRSF1 expression exacerbates mitochondrial dysfunction, elevates reactive oxygen species, and impairs ATP production. Furthermore, RNA immunoprecipitation revealed GRSF1's interaction with superoxide dismutase 2 (SOD2) mRNA, a key antioxidant enzyme, suggesting a mechanism whereby GRSF1 modulates oxidative stress. Downregulation of SOD2 reversed the protective effects of GRSF1 overexpression on mitochondrial function. These insights into the role of GRSF1 in ovarian aging may guide the development of interventions to improve fertility outcomes in advanced age.

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GRSF1 缺乏会削弱衰老颗粒细胞的线粒体功能。
卵巢衰老严重影响生殖潜能,卵母细胞质量和数量明显下降,氧化应激和线粒体功能障碍增加。本研究阐明了富鸟嘌呤核糖核酸序列结合因子1(GRSF1)在卵巢颗粒细胞(GCs)衰老过程中的作用。我们利用试管婴儿患者的临床样本观察到,GCs 中 GRSF1 的明显减少与患者年龄相关。利用 siRNA 介导的基因敲除技术,我们确定 GRSF1 表达的减少会加剧线粒体功能障碍、增加活性氧并损害 ATP 的产生。此外,RNA免疫沉淀显示,GRSF1与超氧化物歧化酶2(SOD2)mRNA(一种关键的抗氧化酶)相互作用,这表明GRSF1调节氧化应激的机制。SOD2的下调逆转了GRSF1过表达对线粒体功能的保护作用。这些关于GRSF1在卵巢衰老中的作用的见解可能会指导干预措施的开发,从而改善高龄患者的生育能力。
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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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