Aim: Rapid revascularization is essential for reducing hypoxic damage and protecting ovarian graft reserve after transplantation. We have previously shown that endothelial activation of Akt1, a key mediator of angiogenesis, promotes angiogenesis in ovarian grafts. Recent studies suggest that simvastatin activates Akt1 and induces angiogenesis. The aim of this study was to evaluate whether simvastatin administration improves ovarian graft vascularization.
Materials and methods: A mouse model of heterotopic ovarian graft transplantation. Ovarian graft revascularization was explored by in vivo dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and fluorescence microscopy. Activated simvastatin (0.1 mg/kg/day) (group A) or saline (group B) were injected to recipient mice (n=7,7), starting from one day prior to ovarian grafting and throughout the following 7 days. Vascular properties of the grafts were estimated from the MRI derived parameters: vascular density (blood volume fraction, fBV) and permeability (PS). The changes in fBV and PS were examined on days 2 and 7 after transplantation, and following superovulation.
Results: Grafts treated with simvastatin improved their mean fBV values by 80% compared to baseline levels on day 2. Mean fBV improved by only 21% in the control group (P<0.05). Furthermore, higher blood vessel density was depicted by fluorescence microscopy in group A following superovulation. PS was lower on day 7 compared to day 2 in both groups, possibly due to accelerated blood vessel maturation at the transplantation site.
Conclusion: Simvastatin therapy, given for 7 days following ovarian transplantation, improves the revascularization and vascular support of ovarian grafts.
