Exosomes derived from hypoxic mesenchymal stem cells restore ovarian function by enhancing angiogenesis

• Hypoxic preconditioning enhances the angiogenic potential of hucMSC-derived exosomes, promoting endothelial cell proliferation, migration, and tube formation in vitro. • In a rat model of premature ovarian failure (POF), hypoxia-pretreated exosomes significantly restore ovarian function by enhancing angiogenesis in vivo. • The therapeutic effect is mediated by exosomal miR-205-5p, which targets the PTEN/PI3K/AKT/mTOR signaling pathway to stimulate angiogenesis. • This study provides a novel cell-free therapeutic approach using stem cell-derived exosomes for the treatment of POF, offering a theoretical basis for clinical translation.