Center of Reproduction and Genetics, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215002, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Jiangsu 210029, China.
Aging (Albany NY). 2020 Feb 10;12(3):2992-3009. doi: 10.18632/aging.102794.
Human placental mesenchymal stem cells (hPMSCs) have the ability to release cytokines and to differentiate into the three germ layers. To date, the relevance of hPMSCs for the treatment of premature ovarian insufficiency (POI) disease through the regulation of oxidative stress is still unclear. Therefore, to evaluate the therapeutic efficiency and investigate the mechanism of hPMSCs, we generated a mouse model of POI and collected human ovarian granule cells (hGCs) from patients with POI. hPMSCs displayed therapeutic effects on POI ovarian function, including recovered follicular numbers and increased expression of oocyte markers. Furthermore, secretion of the cytokine EGF (epidermal growth factor) was higher from hPMSCs than it was from other cells. FACS and Western blot analyses showed that EGF elevated the proliferation and reduced the apoptosis in hGCs. hPMSCs and EGF inhibited oxidative stress levels. Protein assays demonstrated that EGF suppressed oxidative stress by dose-dependently upregulating the expression of the NRF2/HO-1 pathway, and it inhibited the apoptosis by regulating the PTEN/PI3K/AKT pathway. These findings provide an experimental foundation for hPMSCs in improving ovarian function through the secretion of EGF. The mechanism of action of EGF is related to protection from oxidative stress by activation of the NRF2/HO-1.
人胎盘间充质干细胞（hPMSCs）具有释放细胞因子和分化为三个胚层的能力。迄今为止，hPMSCs 通过调节氧化应激对治疗卵巢早衰（POI）疾病的相关性仍不清楚。因此，为了评估 hPMSCs 的治疗效果并研究其作用机制，我们建立了 POI 小鼠模型，并从 POI 患者中收集了人卵巢颗粒细胞（hGCs）。hPMSCs 对 POI 卵巢功能具有治疗作用，包括恢复卵泡数量和增加卵母细胞标志物的表达。此外，hPMSCs 分泌的细胞因子 EGF（表皮生长因子）高于其他细胞。FACS 和 Western blot 分析表明，EGF 可促进 hGCs 的增殖并减少其凋亡。hPMSCs 和 EGF 可抑制氧化应激水平。蛋白分析表明，EGF 通过上调 NRF2/HO-1 通路的表达，以剂量依赖性方式抑制氧化应激，通过调节 PTEN/PI3K/AKT 通路抑制细胞凋亡。这些发现为 hPMSCs 通过分泌 EGF 改善卵巢功能提供了实验基础。EGF 的作用机制与通过激活 NRF2/HO-1 来保护免受氧化应激有关。
