Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway
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View abstract on PubMed
Summary
This summary is machine-generated.This study shows that combining mesenchymal stem cell mitochondria (MSC-Mito) with pyrroloquinoline quinone (PQQ) effectively treats premature ovarian insufficiency (POI). The therapy restores ovarian function by enhancing mitochondrial health and reducing oxidative stress via the SIRT1/ATM/p53 pathway.
Area Of Science
- Reproductive Biology
- Mitochondrial Medicine
- Stem Cell Therapy
Background
- Chemotherapy-induced DNA damage and oxidative stress contribute to premature ovarian insufficiency (POI).
- Mesenchymal stem cell mitochondria (MSC-Mito) show promise for age-related diseases but have limited efficacy alone.
- Pyrroloquinoline quinone (PQQ) is an antioxidant with antiaging and fertility-enhancing properties.
Purpose Of The Study
- To investigate the therapeutic potential of combining MSC-Mito with PQQ for treating POI.
- To elucidate the underlying molecular mechanisms of this combined therapy.
Main Methods
- Established a POI mouse model using cyclophosphamide and busulfan.
- Assessed ovarian function, hormone levels, and oxidative stress markers.
- Utilized Western blotting and immunohistochemistry to analyze SIRT1, PGC-1α, and ATM/p53 pathway proteins.
- Investigated DNA damage and apoptosis in vitro using KGN cells and flow cytometry.
- Employed SIRT1 siRNA to confirm pathway involvement.
Main Results
- Combined MSC-Mito and PQQ treatment significantly restored ovarian function and antioxidant capacity in POI mice.
- The therapy improved estrous cycles and reduced follicle loss.
- In vitro, PQQ enhanced MSC-Mito proliferation, synergistically improving mitochondrial function and reducing oxidative stress.
- The combination therapy promoted mitochondrial biogenesis via SIRT1/PGC-1α and inhibited ATM/p53 activation, reducing DNA damage and apoptosis.
- SIRT1 inhibition reversed the therapeutic effects, confirming pathway mediation.
Conclusions
- PQQ enhances MSC-Mito proliferation, and their combination effectively ameliorates chemotherapy-induced POI.
- The therapeutic mechanism involves the SIRT1/ATM/p53 signaling pathway, promoting mitochondrial health and reducing oxidative stress.
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