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hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway.
Stem Cell Research & Therapy ( IF 7.1 ) Pub Date : 2020-07-03 , DOI: 10.1186/s13287-020-01784-7
Xueyan Lu 1, 2 , Hongchu Bao 3 , Linlu Cui 1, 2 , Wenqian Zhu 1 , Lianshuang Zhang 2 , Zheng Xu 2 , Xuejing Man 3 , Yongli Chu 3 , Qiang Fu 2 , Hongqin Zhang 1, 2
Affiliation  

Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs. The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs. This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

中文翻译:

hUMSC移植通过抑制AMPK / mTOR信号通路的ca-间质细胞自噬来恢复POI大鼠的卵巢功能。

先前对原发性卵巢功能不全(POI)的研究集中于颗粒细胞(GCs),而忽略了卵泡间质细胞(TICs)的作用。本研究旨在通过调节TICs的自噬,探讨人脐带间充质干细胞(hUMSCs)对POI大鼠卵巢功能的保护作用机制。在用顺铂(CDDP)治疗的大鼠中建立了POI模型。将hUMSC通过尾静脉移植到POI大鼠中。酶联免疫吸附测定(ELISA)分析,苏木精和曙红(HE)染色以及免疫组化方法用于测量hUMSC的保护作用。通过免疫荧光,透射电子显微镜(TEM),流式细胞仪(FCM),蛋白质印迹,和实时定量聚合酶链反应(qRT-PCR)。在体内,hUMSC移植可恢复POI大鼠卵巢功能并减轻TICs的凋亡。在体外,hUMSC通过降低氧化应激和调节AMPK / mTOR信号通路来降低TICs的自噬水平,从而减轻TICs的细胞凋亡。这项研究表明,hUMSC通过调节自噬信号通路AMPK / mTOR保护POI中的卵巢功能。
更新日期:2020-07-03
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