原花青素通过调节雌性生殖干细胞中的sirt1-p53-p21信号通路延缓卵巢早衰。
Proanthocyanidins delaying the premature ovarian insufficiency through regulatory sirt1-p53-p21 signaling pathway in female germline stem cells.
作者信息
Wu Wenbo, Bai Mengying, Hong Wenli, Ling Shuyi, Li Yuan, Dai Yuqing, Weng Ruoxin, Wu Haifeng, Ren Chongyang, Zhang Liujuan, Zhou Ziqiong, Zhong Zhisheng, Fu Xinxin, Zheng Yuehui
机构信息
The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033, Guangdong, China.
Guangzhou University of Chinese Medicine, 232 East Outer Ring Road, University Town, Guangzhou, 510006, Guangdong Province, China.
出版信息
J Ovarian Res. 2025 May 10;18(1):97. doi: 10.1186/s13048-025-01661-y.
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 (E) 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.
背景
随着女性年龄增长，其卵巢卵泡池自然衰退。然而，雌性生殖干细胞（FGSCs）具有独特的分化为卵母细胞并持续自我更新的能力，通过补充原始卵泡池提供了一种延缓卵巢衰老的有效方法。因此，激活FGSCs对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，原花青素是一种天然抗氧化剂，具有对雄性和雌性生殖有益的抗衰老和抗炎特性。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增加了小鼠原始卵泡、初级卵泡、黄体的数量，同时减少了囊性卵泡，并提高了雌二醇（E）水平以及抗苗勒管激素（AMH）浓度水平。此外，PACs通过上调FGSCs特异性标志物如MVH和OCT4的mRNA和蛋白质表达，同时通过激活沉默信息调节因子1（Sirt1）信号通路下调p53/p21，以时间和剂量依赖性方式显著促进FGSCs增殖。发现Sirt1抑制剂EX527可阻碍PACs对FGCSs的作用。
结论
PACs通过调节涉及FGSCs的Sirt1-p53-p21信号通路延缓卵巢早衰（POI）。
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