Extracellular matrix: new insights into its role in female reproductive aging and potential therapeutic strategies

Extracellular matrix (ECM), once regarded as a passive structural scaffold, is now recognized as a key hallmark of aging. In the context of female reproductive aging, ECM remodeling acts as a pivotal driver of functional deterioration. This review outlines how age-associated ECM alterations, including collagen cross-linking, elastin degradation, and perturbed biomechanics, orchestrate ovarian aging through the mechanical activation of Hippo signaling, compromise endometrial receptivity via dysregulated matrix metalloproteinase activity, and impair embryo invasion by altering ligand presentation. We also discuss emerging ECM-targeted strategies, such as decellularized scaffolds, engineered hydrogels, and 3D-bioprinted matrices, which have demonstrated potential for rejuvenating reproductive function in preclinical models. Furthermore, matrisome-based biomarkers provide novel prognostic insights into reproductive outcomes. Collectively, these advances identify the ECM as a promising target for innovative, non-hormonal interventions aimed at extending female reproductive longevity.