The prospect of ovarian rejuvenation offers the tantalising prospect of treating age-related declines in fertility or in pathological conditions such as premature ovarian failure. The concept of ovarian rejuvenation was invigorated by the indication of the existence of oogonial stem cells (OSCs), which have been shown experimentally to have the ability to differentiate into functional follicles and generate oocytes; however, their clinical potential remains unknown.  Furthermore, there is now growing interest in performing ovarian rejuvenation in situ.  One proposed approach involves injecting the ovary with platelet rich plasma (PRP). PRP is a component of blood that remains after the in vitro removal of red and white blood cells.  It contains blood platelets, tiny anucleate cells of the blood, which are responsible for forming a thrombus to prevent bleeding.  In addition, PRP contains an array of cytokines and growth factors, as well as a number of small molecules.  The utility of PRP has been investigated in a range of regenerative medicine approaches and has been shown to induce differentiation of a range of cell types, presumably through the action of cytokines.  A handful of case reports have described the use of PRP injections into the ovary in the human, and while these clinical data report promising results, knowledge on the mechanisms and safety of PRP injections into the ovary remain limited.  In this article, we summarise some of the physiological detail of platelets and PRP, before reviewing the existing emerging literature in this area. We then propose potential mechanisms by which PRP may be eliciting any effects before reflecting on some considerations for future studies in the area. Importantly, on the basis of our existing knowledge, we suggest that immediate use of PRP in clinical applications is perhaps premature and further fundamental and clinical research on the nature of ovarian insufficiency, as well as the mechanism by which PRP may act on the ovary, is needed to fully understand this promising development.

Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation and inhibition. We hypothesised that Nitric oxide (NO), a platelet inhibitor, can modulate the actin cytoskeleton reversing platelet spreading, and therefore reduce the capability of thrombi to withstand a high shear environment. Our data demonstrates that GSNO, DEANONOate, and a PKG-activating cGMP analogue reversed stress fibre formation and increased actin nodule formation in adherent platelets. This effect is sGC dependent and independent of ADP and thromboxanes. Stress fibre formation is a RhoA dependent process and NO induced RhoA inhibition, however, it did not phosphorylate RhoA at ser188 in spread platelets. Interestingly NO and PGI2 synergise to reverse stress fibre formation at physiologically relevant concentrations. Analysis of high shear conditions indicated that platelets activated on fibrinogen, induced stress fibre formation, which was reversed by GSNO treatment. Furthermore, preformed thrombi on collagen post perfused with GSNO had a 30% reduction in thrombus height in comparison to the control. This study demonstrates that NO can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling excessive thrombosis.

Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear. Exploration of the molecular mechanisms underpinning this effect revealed that PGI2 reversed stress fibre formation in adherent platelets, reduced platelet spreading, whilst simultaneously promoting actin nodule formation. The effects of PGI2 on stress fibres were mimicked by the adenylyl cyclase activator forskolin and prevented by inhibitors of protein kinase A (PKA). Stress fibre formation is a RhoA dependent process and we found that treatment of adherent platelets with PGI2 caused inhibitory phosphorylation of RhoA, reduced RhoA GTP-loading and reversal of myosin light chain phosphorylation. Phospho-RhoA was localised in actin nodules with PKA type II and a number of other phosphorylated PKA substrates. This study demonstrates that PGI2 can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling thrombosis.