Human platelet-rich plasma promotes the primordial follicle activation through the PI3K/Akt signaling pathway

The activation of dormant primordial follicles is a promising method for rescuing the infertility of aged women and premature ovarian insufficiency (POI) patients. Accumulating evidences in both human and animal suggest that human platelet-rich plasma (hPRP) has the ability to recover ovarian function and promote follicle growth, however the underlying mechanisms remain unclear. In the current study, we revealed that hPRP promoted the activation of primordial follicles and the proliferation of granulosa cells. hPRP treatments significantly increased the levels of phosphorylated protein kinase B (Akt) and forkhead Box O3a (FOXO3a), and the number of oocytes with FOXO3a nuclear export. The hPRP-induced primordial follicle activation could be blocked by LY294002, the inhibitor of PI3K/Akt. By in vivo injection newborn mice model and in vitro culture human ovarian fragments, hPRP was further proved to be effective in the activation of primordial follicles. Taken together, our results suggest that hPRP can promote the primordial follicle activation through the PI3K/Akt pathway. Our results provide a theoretical basis for the clinical application of hPRP in aged women and POI patients. Overall design: We selected thrombin to activated hPRP, the ovaries of newborn 3-day-old mice were cultured in vitro with concentration gradient and the optimal hPRP working concentration was selected from different concentrations of hPRP to promote the activation of primordial follicles. The effect of PRP on primordial follicle activation and its possible mechanism were studied by in vitro and in vivo mouse models, human ovarian tissue culture models and transcriptome sequencing.