Simvastatin and EPO in feline ovarian grafting: Distinct effects on cell and follicle survival

This study aimed to examine the effects of simvastatin and erythropoietin on follicular survival and revascularization after subcutaneous autotransplantation of cryopreserved ovarian tissue in domestic cats as a model for endangered felids. Twelve healthy domestic cats were randomly divided into three groups: Control, Simvastatin (SIM), and Erythropoietin (EPO). The SIM group received a single oral dose of 5 mg/kg 4 h prior to ovariohysterectomy, while the EPO group received subcutaneous injections of 500 IU/Kg for 7 consecutive days prior to grafting. Frozen/thawed ovarian fragments were grafted into the upper neck of the queens and removed after 7, 14, 21, 28, 49 and 63 days. There was no significant difference in the vascularization area among the groups on any post-transplant day. Treatment with SIM and EPO resulted in generally smaller areas of inflammation in the tissue. The SIM group presented six Ki67-positive, morphologically normal growing follicles on days 49 and 63, significantly more than the Control group (2 found only on D7) and the EPO group (1 found on D14). The EPO group showed a significantly larger number of follicle-like structures, which were composed mainly of proliferative granulosa cells with no oocyte. In conclusion, these results suggest that EPO selectively supports somatic cell survival and SIM may promote the long-term viability and growth of residual follicles. Future efforts should focus on optimizing the dose, route, timing of administration, and combination therapies to effectively harness these beneficial effects to improve ovarian tissue cryopreservation and transplantation outcomes in felids.