hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats
Abstract Background One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunctio...
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BMC
2025-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04396-1 |
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| author | Yu Tang Yu He Xingyu Huo Juntong Chen Maojiao Qian Haoyu Huang Yixuan Meng Lianshuang Zhang Feibo Xu Yukun Zhang Hongchu Bao Yanlian Xiong |
| author_facet | Yu Tang Yu He Xingyu Huo Juntong Chen Maojiao Qian Haoyu Huang Yixuan Meng Lianshuang Zhang Feibo Xu Yukun Zhang Hongchu Bao Yanlian Xiong |
| author_sort | Yu Tang |
| collection | DOAJ |
| description | Abstract Background One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunction brought on by POI. However, its therapeutic mechanism is still unclear and needs further exploration. Methods POI model was established by intraperitoneal injection of cyclophosphamide (CTX) in female Wistar rats. These POI rats were treated with hUMSC-Exos for one week. In addition to in vivo experiments, in vitro POI models were also established. In vitro experiments, theca interstitial cells (TICs) treated with CTX were exposed to normal as well as let-7a-5p inhibitory hUMSC-Exos. The ovary structure, morphology, endocrine function, and reproductive ability of POI rats were observed by H&E staining and ELISA. Western blot, immunofluorescence staining (IF), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the autophagy-related indexes in ovary and TICs of POI rats in each group. Results CTX induced abnormalities of ovarian morphology, structure, endocrine, and reproductive function in rats, and accompanied by autophagy of TICs. Notably, hUMSC-Exos diminishes ovarian structural and functional damage in POI rats and TICs autophagy via targeting the AMPK/mTOR pathway. Furthermore, downregulating let-7a-5p in hUMSC-Exos weakened their ability to prevent TICs autophagy. Conclusions Overall, the findings suggested that hUMSC-Exos improves ovarian function in POI rats by inhibiting TICs autophagy via the let-7a-5p/AMPK/mTOR pathway. Our study provided further evidence that POI patients can benefit from hUMSC-Exos-mediated therapy. |
| format | Article |
| id | doaj-art-ff56c8624d1849028858b86f7fdccea7 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-ff56c8624d1849028858b86f7fdccea72025-08-20T03:25:12ZengBMCStem Cell Research & Therapy1757-65122025-06-0116111710.1186/s13287-025-04396-1hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI ratsYu Tang0Yu He1Xingyu Huo2Juntong Chen3Maojiao Qian4Haoyu Huang5Yixuan Meng6Lianshuang Zhang7Feibo Xu8Yukun Zhang9Hongchu Bao10Yanlian Xiong11Xu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityReproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityXu Rongxiang Regenerative Medicine Research Center, School of Basic Medicine, Binzhou Medical UniversityAbstract Background One major factor contributing to infertility in women of childbearing age is premature ovarian insufficiency (POI). Exosomes produced from human umbilical cord mesenchymal stem cells (hUMSC-Exos) have drawn a lot of attention lately as a potential treatment for ovarian dysfunction brought on by POI. However, its therapeutic mechanism is still unclear and needs further exploration. Methods POI model was established by intraperitoneal injection of cyclophosphamide (CTX) in female Wistar rats. These POI rats were treated with hUMSC-Exos for one week. In addition to in vivo experiments, in vitro POI models were also established. In vitro experiments, theca interstitial cells (TICs) treated with CTX were exposed to normal as well as let-7a-5p inhibitory hUMSC-Exos. The ovary structure, morphology, endocrine function, and reproductive ability of POI rats were observed by H&E staining and ELISA. Western blot, immunofluorescence staining (IF), and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate the autophagy-related indexes in ovary and TICs of POI rats in each group. Results CTX induced abnormalities of ovarian morphology, structure, endocrine, and reproductive function in rats, and accompanied by autophagy of TICs. Notably, hUMSC-Exos diminishes ovarian structural and functional damage in POI rats and TICs autophagy via targeting the AMPK/mTOR pathway. Furthermore, downregulating let-7a-5p in hUMSC-Exos weakened their ability to prevent TICs autophagy. Conclusions Overall, the findings suggested that hUMSC-Exos improves ovarian function in POI rats by inhibiting TICs autophagy via the let-7a-5p/AMPK/mTOR pathway. Our study provided further evidence that POI patients can benefit from hUMSC-Exos-mediated therapy.https://doi.org/10.1186/s13287-025-04396-1POIhUMSC-ExosTheca interstitial cellslet-7a-5pAutophagy |
| spellingShingle | Yu Tang Yu He Xingyu Huo Juntong Chen Maojiao Qian Haoyu Huang Yixuan Meng Lianshuang Zhang Feibo Xu Yukun Zhang Hongchu Bao Yanlian Xiong hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats Stem Cell Research & Therapy POI hUMSC-Exos Theca interstitial cells let-7a-5p Autophagy |
| title | hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats |
| title_full | hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats |
| title_fullStr | hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats |
| title_full_unstemmed | hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats |
| title_short | hUMSC-derived exosomes alleviate follicular interstitial cell autophagy by let-7a-5p/AMPK/mTOR axis in POI rats |
| title_sort | humsc derived exosomes alleviate follicular interstitial cell autophagy by let 7a 5p ampk mtor axis in poi rats |
| topic | POI hUMSC-Exos Theca interstitial cells let-7a-5p Autophagy |
| url | https://doi.org/10.1186/s13287-025-04396-1 |
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