Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells.

IF 3.8 3区医学 Q1 REPRODUCTIVE BIOLOGY

Journal of Ovarian Research Pub Date : 2025-05-10 DOI:10.1186/s13048-025-01661-y

Wenbo Wu, Mengying Bai, Wenli Hong, Shuyi Ling, Yuan Li, Yuqing Dai, Ruoxin Weng, Haifeng Wu, Chongyang Ren, Liujuan Zhang, Ziqiong Zhou, Zhisheng Zhong, Xinxin Fu, Yuehui Zheng

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引用次数: 0

Abstract

Background: As women age, their ovarian follicle pool naturally declines. However, female germline stem cells (FGSCs) possess a unique ability to differentiate into oocytes and continuously self-renew, providing an effective means of delaying ovarian aging by replenishing the primordial follicle pool. Therefore, activating FGSCs is critical in reshaping and safeguarding ovarian function.

Methods: In this study, we investigated the biological activity of proanthocyanidins (PACs), natural antioxidants that exhibit anti-aging and anti-inflammatory properties beneficial for both male and female reproduction. Our in vivo and in vitro experiments demonstrate that PACs promote FGSCs proliferation while delaying ovarian aging.

Results: PACs increase the number of primordial follicles, primary follicles, corpus luteum while reducing cystic follicles, and elevate estradiol (E₂) levels along with anti-mullerian hormone (AMH) concentration levels in mice. Additionally, PACs significantly boost FGSCs proliferation time- and dose-dependently by upregulating mRNA & protein expressions for FGSCs-specific markers such as MVH and OCT4 while downregulating p53/p21 via activation of silent information regulator 1(Sirt1) signaling pathway. The effects of PACs on FGCSs were found to be impeded by the Sirt1 inhibitor EX527.

Conclusion: PACS delay premature ovarian insufficiency (POI) through regulating the Sirt1-p53-p21 signaling pathway involving FGSCs.

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原花青素通过调节雌性种系干细胞sirt1-p53-p21信号通路延缓卵巢功能不全。

背景：随着女性年龄的增长，她们的卵巢卵泡池自然减少。然而，女性生殖系干细胞（FGSCs）具有独特的分化成卵母细胞并不断自我更新的能力，通过补充原始卵泡池提供了一种有效的延缓卵巢衰老的手段。因此，激活FGSCs对于重塑和保护卵巢功能至关重要。方法：在本研究中，我们研究了原花青素（PACs）的生物活性，这是一种具有抗衰老和抗炎特性的天然抗氧化剂，对雄性和雌性生殖都有益。我们的体内和体外实验表明，PACs促进FGSCs增殖，同时延缓卵巢衰老。结果：PACs使小鼠原始卵泡、初级卵泡、黄体数量增加，囊性卵泡减少，雌二醇（E2）水平升高，抗苗勒管激素（AMH）水平升高。此外，PACs通过上调FGSCs特异性标志物（如MVH和OCT4）的mRNA和蛋白表达，同时通过激活沉默信息调节因子1（Sirt1）信号通路下调p53/p21，从而显著促进FGSCs的增殖，这种方式具有时间和剂量依赖性。发现PACs对fgcs的作用被Sirt1抑制剂EX527阻碍。结论：PACS通过调节涉及FGSCs的Sirt1-p53-p21信号通路，延缓卵巢功能不全（POI）。

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

Journal of Ovarian Research REPRODUCTIVE BIOLOGY-

CiteScore

6.20

自引率

2.50%

发文量

125

审稿时长

>12 weeks

期刊介绍： Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ. Topical areas include, but are not restricted to: Ovary development, hormone secretion and regulation Follicle growth and ovulation Infertility and Polycystic ovarian syndrome Regulation of pituitary and other biological functions by ovarian hormones Ovarian cancer, its prevention, diagnosis and treatment Drug development and screening Role of stem cells in ovary development and function.