| Abstract: |
Ovarian aging and poor ovarian response (POR) to controlled ovarian stimulation represent critical clinical challenges in reproductive medicine, affecting an estimated 9–24% of women undergoing in vitro fertilization (IVF) cycles. The mesenchymal stem cell (MSC) secretome encompassing growth factors, cytokines, exosomes, and extracellular vesicles has emerged as a promising cell-free approach to restore ovarian function. This study applies a systems-biology framework to map the molecular interactions of the MSC secretome with the aging ovarian microenvironment, focusing on granulosa cell survival, follicular reserve maintenance, and hormonal restoration in POR patients. Key bioactive components, including VEGF, HGF, IGF-1, TGF-β, and exosomal miRNAs, were integrated with central regulatory networks spanning the PI3K/AKT/mTOR, Wnt/β-catenin, and MAPK/ERK signaling cascades. The hypothesis posits that network-level modulation via MSC secretome delivery can attenuate follicular atresia and improve oocyte quality in POR patients by simultaneously activating anti-apoptotic, pro-angiogenic, and anti-inflammatory pathways. Data-supported findings from proteomic profiling, pathway enrichment analyses, and clinical ovarian reserve studies confirm a multi-target mechanistic basis for MSC secretome therapy. These results provide a robust translational foundation for deploying MSC-conditioned medium and extracellular vesicles in clinical fertility management. |
