Roles of exosomes in microenvironment-related premature ovarian insufficiency: mechanisms and therapeutic intervention

Exosomes are nanoscale vesicles that traffic bioactive cargo and modulate cell-cell communication within the ovarian niche. They are pivotal mediators in ovarian microenvironment-related premature ovarian insufficiency (omePOI): pathogenic exosomes propagate injury, whereas therapeutic Exosomes restore homeostasis to shape the niche and influence disease onset and course. However, omePOI still lacks sensitive predictive biomarkers and disease-modifying therapies; moreover, the complexity of the ovarian niche-encompassing extracellular matrix, stromal and immune compartments, vasculature, and metabolic-redox balance-poses substantial translational challenges. In this Review, we first summarize the current clinical challenges in diagnosing and managing omePOI. We then focus on reported correlations between exosomal alterations and omePOI, and postulate mechanisms by which these vesicles influence disease biology across apoptosis/mitochondrial injury, senescence, inflammation and innate-adaptive crosstalk, angiogenesis, fibrosis/extracellular matrix, and metabolic-redox pathways. Finally, we highlight the potential value of exosomal changes as biomarkers for predicting omePOI and discuss exosomal interventions, including mesenchymal stromal cell-derived and engineered Exosomes, as well as exosome-biomaterial composites together with design principles from ovarian tissue engineering.