hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway

hUMSC 移植通过 AMPK/mTOR 信号通路抑制卵泡膜间质细胞自噬,恢复 POI 大鼠的卵巢功能

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作者:Xueyan Lu, Hongchu Bao, Linlu Cui, Wenqian Zhu, Lianshuang Zhang, Zheng Xu, Xuejing Man, Yongli Chu, Qiang Fu, Hongqin Zhang

Background

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.

Conclusion

This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

Methods

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).

Results

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.

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