Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival

Resveratrol Plays a Protective Role against Premature Ovarian Failure and Prompts Female Germline Stem Cell Survival
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白藜芦醇对卵巢早衰具有保护作用,并促进女性生殖干细胞存活

DOI:
10.3390/ijms20143605
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发表时间:
2019-07-02
影响因子:
5.6
通讯作者:
Pan, Zezheng
Pan, Zezheng
中科院分区:
生物学2区
文献类型:
--
作者:
Jiang, Yu;Zhang, Zhaoyuan;Pan, Zezheng

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本研究旨在从组织和细胞水平探讨白藜芦醇(RES)对卵巢早衰(POF)的保护作用及对女性生殖干细胞(FGSCs)增殖的影响。用RES灌洗POF小鼠,并将POF卵巢与RES和/或GANT 61在体外共培养。用白消安、RES和/或GANT 61预处理FGSCs,与RES预处理的M1巨噬细胞共培养,测定小鼠体重、卵巢重量和卵泡数。评估卵巢功能、抗氧化应激、炎症和FGSC存活。RES能显著增加卵巢和卵巢的重量,增加卵泡数,降低卵泡闭锁率。在体内和体外,RES处理后检测到较高水平的Mvh,Oct 4,SOD 2,GPx和CAT。RES处理组卵巢中TNF-α和IL-6浓度显著降低,IL-10浓度显著升高。在FGSC中,RES组测得较高的Mvh、Oct 4和SOD 2浓度以及较低的TNF-α、IL-6和MDA浓度。阻断Hh信号通路可逆转RES对FGSC的保护作用。综上所述,RES可通过减轻氧化应激、炎症反应及Hh信号通路等机制,有效改善POF模型的卵巢功能和FGSC的增殖能力,提示RES是一种潜在的抗POF药物,可促进FGSC的存活。
This study was designed to investigate the protective effect of resveratrol (RES) on premature ovarian failure (POF) and the proliferation of female germline stem cells (FGSCs) at the tissue and cell levels. POF mice were lavaged with RES, and POF ovaries were co-cultured with RES and/or GANT61 in vitro. FGSCs were pretreated with Busulfan and RES and/or GANT61 and co-cultured with M1 macrophages, which were pretreated with RES. The weights of mice and their ovaries, as well as their follicle number, were measured. Ovarian function, antioxidative stress, inflammation, and FGSCs survival were evaluated. RES significantly increased the weights of POF mice and their ovaries as well as the number of follicles, while it decreased the atresia rate of follicles. Higher levels of Mvh, Oct4, SOD2, GPx, and CAT were detected after treatment with RES in vivo and in vitro. RES treatment resulted in significantly lower TNF-α and IL-6 concentrations and an obviously higher IL-10 concentration in the ovaries. In FGSCs, higher Mvh, Oct4, and SOD2 concentrations and lower TNF-α, IL-6, and MDA concentrations were measured in the RES group. Blockage of the Hh signaling pathway reversed the protective effect of RES on FGSCs. In conclusion, RES effectively improved the ovarian function of the POF model and the productive capacity of FGSCs via relieving oxidative stress and inflammation and a mechanism involving the Hh signaling pathway, suggesting that RES is a potential agent against POF and can aid in the survival of FGSCs.