• hUMSC-derived exosomes (hUMSC-Exos) effectively alleviate ovarian structural and functional damage in a rat model of premature ovarian insufficiency (POI) induced by cyclophosphamide.
• The therapeutic mechanism involves inhibition of theca interstitial cell (TIC) autophagy via the let-7a-5p/AMPK/mTOR signaling pathway.
• Downregulation of let-7a-5p in hUMSC-Exos diminishes their protective effect, confirming the crucial role of this miRNA in mediating the therapy.
• These findings provide strong preclinical evidence supporting hUMSC-Exos as a promising cell-free therapeutic strategy for POI patients.