G-CSF-mobilized Peripheral Blood Mononuclear Cells Combined with Platelet-rich Plasma Restored the Ovarian Function of aged rats via angiogenesis and glycolysis modulation

Background: Regenerative medicine with peripheral blood mononuclear cells (PBMCs) transplantation sheds light on the issue of premature ovarian insufficiency (POI). However, the efficiency of PBMCs treatment in patients with natural ovarian aging (NOA) remain unclear. Methods 13-month-old female Sprague–Dawley (SD) rats were used to verify NOA model. Seventy-two NOA rats were randomly divided into three groups: the NOA control group, PBMCs group, and PBMCs + PRP group. PBMCs and PRP were transplanted by intraovarian injection. The effects of ovarian function and fertility ability were measured after transplantation. Results Transplantation of PBMCs could restoration of the normal estrus cycle, consistent with recovery of serum sex hormone levels, increased follicle numbers at all stages, and restoration of fertility by facilitating pregnancy and live birth. Moreover, when combined with PRP injection, these effects were more significant. The male-specific SRY gene was detected in the ovary at all four time points, suggesting PBMCs continuously survived and functioned in NOA rats. In addition, after PBMCs treatment, the expression of the angiogenesis-related and glycolysis-related markers in ovarian were upregulated, which indicated that these effects were associated with angiogenesis and glycolysis. Conclusions PBMCs transplantation restore the ovarian functions and fertility of NOA rats by increasing ovarian vascularization, folliculogenesis and glycolysis, and PRP could enhance the efficiency.