Platelet-rich plasma and folliculogenesis: a systematic mechanistic review and computational pathway analysis.

INTRODUCTION: Platelet-rich plasma (PRP) has been proposed as a potential intervention for promoting ovarian follicular development. However, its underlying biological mechanisms remain unclear. This study investigated whether the mechanisms through which PRP may influence follicular development are consistent with previously established regulatory mechanisms of human folliculogenesis. METHODS: A systems biology approach was used to examine the mechanistic relationships between growth factors present in PRP and known regulators of human follicular development. Gene databases were compared, and pathway enrichment analysis and integrated network modeling were performed to identify shared signaling pathways and patterns of molecular connectivity. RESULTS: Although there was limited overlap between the two gene databases, substantial convergence was observed in pathway enrichment and integrated network modeling. This convergence involved receptor tyrosine kinase-centered intracellular signaling pathways, particularly the PI3K-AKT and MAPK pathways. Network topology demonstrated coherent connectivity between extracellular growth factors and established survival and proliferation signaling axes. However, no overlap was identified between genes associated with PRP and genes encoding oocyte-specific transcriptional regulators involved in primordial follicle formation and differentiation. DISCUSSION: These findings support a model in which PRP does not replace the endogenous transcriptional program governing follicular development. Instead, PRP may increase upstream growth factor signaling and enhance intrinsic survival and proliferation pathways within the ovarian microenvironment. This systems-level framework provides mechanistic insight into the biological plausibility of PRP use in reproductive medicine and offers a rational basis for targeted experimental validation.