ArticleStem cell reviews and reports2023
hUMSCs Transplantation Regulates AMPK/NR4A1 Signaling Axis to Inhibit Ovarian Fibrosis in POI Rats.
Article in Stem cell reviews and reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 25 citations in OpenAlex.
- Umbilical cord mesenchymal stem cells and their extracellular vesicles attenuate cryopreservation-induced ovarian injury via the suppression of ferroptosis in an in vitro culture system.Materials today. Bio · 2026Article
- hUCMSCs restore ovarian function via angiopoietin 1/2 rebalance in POI rats.Journal of ovarian research · 2025Article
- Primary human ovarian interstitial cells contribute to murine follicle growth through follicle-interstitial paracrine crosstalk.Research square · 2025Article
- Optimal transplantation strategies for stem cell treatment in premature ovarian failure: a network meta-analysis.Stem cell research & therapy · 2025Review
- Review
- Advances in mesenchymal stem cell and exosome-based therapies for aging and age-related diseases.Stem cell research & therapy · 2025Review
- Stem cell treatments for female reproductive disorders: a comprehensive review.Journal of ovarian research · 2025Review
- Precision medicine in premature ovarian insufficiency: a focus on the precision therapeutic strategies for mesenchymal stem cells.Stem cell research & therapy · 2025Review
- Functional and Genetic Insights into the Role of theAnimals : an open access journal from MDPI · 2025Article
- Mast cell tryptase-PAR2 axis promotes ovarian fibrosis through RNF152-mediated stabilization of Bcl-xL.Journal of ovarian research · 2025Article
- Cardioprotective effects of hUCMSCs-Exosi-EGR1 MN patch in MI/RI by modulating oxidative stress and mitophagy.Materials today. Bio · 2025Article
- Extracellular vesicles in stem cell-based gonadal regeneration: mechanisms, therapeutic potential, and translational challenges.Frontiers in veterinary science · 2025Review
- SPDEF ameliorates UUO-induced renal fibrosis by transcriptional activation of NR4A1.Molecular medicine (Cambridge, Mass.) · 2024Article
- Intraovarian injection of 3D-MSC-EVs-ECM gel significantly improved rat ovarian function after chemotherapy.Reproductive biology and endocrinology : RB&E · 2024Article
- Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage.Human reproduction update · 2024Review
- hUMSCs restore ovarian function in POI mice by regulating GSK3β-mediated mitochondrial dynamic imbalances in theca cells.Scientific reports · 2024Article
- Ovarian fibrosis: molecular mechanisms and potential therapeutic targets.Journal of ovarian research · 2024Review
- Umbilical cord mesenchymal stem cells: A novel approach to intervention of ovarian ageing.Regenerative therapy · 2024Review
- The remodeling of ovarian function: targeted delivery strategies for mesenchymal stem cells and their derived extracellular vesicles.Stem cell research & therapy · 2024Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe mechanism of human Umbilical Cord Mesenchymal Stem Cells (hUMSCs) transplantation to improve ovarian function in the rats with Premature Ovarian Insufficiency (POI) is still unclear. The aim of this study is to investigate the signal axis mechanism that is involved in the ovarian function recovery of POI rats following hUMSCs transplantation.
methodsThe rat model with POI was established by intraperitoneal injection of cisplatin. The hUMSCs were transplanted by caudal vein injection into POI rats. Hematoxylin-eosin (H&E) staining was performed to examine the morphology of rat ovarian tissue. Masson staining, Sirus red staining and immunofluorescence were used to observe the fibrosis extent of ovarian tissue. The levels of serum sex hormones and the expression of fibrosis related markers in ovarian tissues were measured by enzyme-linked immunosorbent assay (ELISA). The expression of NR4A1, Phospho-NR4A1 and AMP-activated protein kinase (AMPK) signaling in rat ovarian tissues was measured by immunohistochemistry and immunofluorescence. The role of AMPK/NR4A1 signaling axis in the regulation of ovarian function recovery in POI rats following hUMSCs transplantation was further investigated by adenovirus and siRNA intervention in isolated stromal cells.
resultsThe results showed that the hUMSCs transplantation significantly inhibited ovarian tissue fibrosis and restored the ovarian function in POI rats. The level of NR4A1 and AMPK expression in ovarian tissue of POI rats after hUMSCs transplantation was significantly increased compared with the control group. In the cultured ovarian stromal cells, the similar results were obtained on the expression of NR4A1 and its regulation on fibrosis related molecular markers in Cisplatin (CDDP) damaged stromal cells following hUMSCs supernatant treatment. Both hUMSCs supernatant treatment and the addition of AMPK inhibitors increased NR4A1 expression in stromal cells. And after NR4A1 molecular intervention, fibrosis-related indicators in stromal cells changed. The data suggests that the AMPK/NR4A1 signaling axis is involved in the ovarian function changes in POI rats following hUMSCs transplantation.
conclusionThe data from this study indicate that the inhibition of tissue fibrosis and recovery of ovarian function is regulated by AMPK/NR4A1 signaling axis in POI rats following hUMSCs transplantation.
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