Growth factors, gene activation and cell recruitment: From intraovarian condensed platelet cytokines to de novo oocyte development

Interest in decelerating or reversing reproductive aging is unlikely to diminish in the era of molecular genetics. For the adult human ovary, meeting the challenge of menopause without synthetic hormone replacement has now moved beyond proof-of-concept, as shown from treatments validated with standard metabolic markers and ovarian reserve estimates. However, without proper recruitment and differentiation of oocytes, such outcomes would be impossible. The full inventory of factors required for such folliculogenesis is not yet final, but growth differentiation factor-9, transforming growth factor-beta1, vascular endothelial growth factor, and insulin-like growth factor-1 are consistently identified as relevant. Platelet-derived growth factor and, more recently, bone morphogenic proteins are also central to cell migration, vascular support, and general ovarian function. Interestingly, when cells secreting these moieties are surgically grafted near undifferentiated oocyte stem precursors, the latency phase transitions to delineate follicle development and restoration of reproductive capacity. Direct intraovarian injection of condensed platelet-derived cytokines (a platelet-rich plasma/PRP product) likewise enables return of menses, ovulation, and term live birth.This report extends our previous work on the proangiogenic effects of intraovarian PRP by connecting clinical responses to specific cytokine-dependent gene activation pathways likely needed to induce oocyte differentiation.Ovarian rejuvenation is a promising new application for platelet-rich plasma and/or condensed plasma cytokines of platelet origin, which are injected into older ovarian tissue.