Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China.
Fuzhou Medical College of Nanchang University, Nanchang 344000, Jiangxi Province, China.
Int J Mol Sci. 2019 Jul 23;20(14):3605. doi: 10.3390/ijms20143605.
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.
本研究旨在探讨白藜芦醇（RES）在组织和细胞水平上对卵巢早衰（POF）和雌性生殖干细胞（FGSCs）增殖的保护作用。将 RES 灌洗 POF 小鼠，将 RES 与 GANT61 共同孵育 POF 卵巢。用白消安和 RES 预处理 FGSCs，并用预处理 RES 的 M1 巨噬细胞共同培养。测量小鼠及其卵巢的重量和卵泡数量。评估卵巢功能、抗氧化应激、炎症和 FGSCs 存活情况。RES 显著增加 POF 小鼠及其卵巢的重量和卵泡数量，同时降低卵泡闭锁率。体内和体外 RES 处理后，Mvh、Oct4、SOD2、GPx 和 CAT 的水平升高。RES 处理后，卵巢中 TNF-α 和 IL-6 浓度降低，IL-10 浓度升高。在 FGSCs 中，RES 组 Mvh、Oct4 和 SOD2 浓度升高，TNF-α、IL-6 和 MDA 浓度降低。阻断 Hh 信号通路会逆转 RES 对 FGSCs 的保护作用。总之，RES 通过缓解氧化应激和炎症以及涉及 Hh 信号通路的机制，有效改善 POF 模型的卵巢功能和 FGSCs 的生殖能力，表明 RES 是一种治疗 POF 的潜在药物，可有助于 FGSCs 的存活。
