Multichannel Recovery Potential with Activated Autologous Intraovarian Platelet-Rich Plasma and Its Derivatives

Abstract

Platelet-rich plasma (PRP) is an 'orthobiologic' with recognized roles in plastic surgery, musculoskeletal disorders, dentistry, dermatology, and more recently, 'ovarian rejuvenation'. Intraovarian PRP involves a complex secretome discharged after platelet activation, comprising multiple cytokine mediators delivered surgically to older or inactive ovarian tissue. Loss of oocyte meiotic fidelity and impaired fertilization accompanying advanced maternal age are already managed by IVF, but only with eggs provided by younger donors. However, if the observed effect of rectifying embryo ploidy error can be proven beyond case reports and small series, activated PRP (or its condensed plasma cytokines) would deliver a welcome therapeutic disruption that is difficult to overstate. Because shortcomings in ovarian function are presently addressed mainly by pharmacological approaches (i.e., via recombinant gonadotropins, GnRH analogs, or luteal support), autologous PRP would represent an unusual departure from these interventions. Given the diversity of platelet cargo proteins, the target response of intraovarian PRP is probably not confined to oocytes or follicles. For example, PRP manipulates signal networks driving improved perfusion, HOX regulation, N-glycan post-translational modification, adjustment of voltage-gated ion channels, telomere stabilization, optimization of SIRT3, and ribosome and mitochondria recovery in older oocytes. While multichannel signals operating on various pathways are not unique to reproductive biology, in intraovarian PRP this feature has received little study and may help explain why its standardization has been difficult. Against this background, our report examines the research themes considered most likely to shape clinical practice.

Keywords: PRP; aging; cell signaling; cytokines; infertility; menopause; ovary.

Figure 1

Fresh autologous platelets (R) are activated (R′) via calcium-based reagent, discharging numerous platelet-derived growth factors and cytokines available for intraovarian injection. EGF can exert a stabilizing effect on telomeres (F), and angiogenesis (B) promoted by VEGF permits general tissue support via improved perfusion. Regulators of HOX loci (H) may include upstream PRP elements, but stemness traits are partially under TGF-β1 control [38]. PRP components coordinate post-translational modifications, such as N-glycan biosynthesis (N) and optimization of SIRT3 (S), as well as improving mitochondrial/ribosomal metabolism (R/M). Ion channel regulation (E) may be an additional role for intraovarian PRP. While operating independent of latent subcapsular ovarian stem cells (A), PRP may deliver secondary actions () to commit undifferentiated progenitors to an oocyte lineage.