Administration of nebivolol after subcutaneous ovarian autotransplantation improves neoangiogenesis, follicular survival, and growth in mice

CONTEXT: As ovarian transplantation is performed without blood vessel anastomosis, its main limitation is ischemia. Nitric oxide (NO) has pro-angiogenic and antiapoptotic effects, and nebivolol, a selective β1-blocker with NO-inducing activity, may be a potential drug to improve graft survival. AIM: To evaluate the effect of nebivolol treatment on follicular growth and angiogenesis in murine autotransplanted ovaries. METHODS: Animals were divided into the following two experiments: ovaries were transplanted either subcutaneously or into the renal capsule, and animals were treated with nebivolol (100 mg/kg intraperitoneally) for five consecutive days post-transplantation. Follicular numbers, morphometry, neovascularization, and blood perfusion were evaluated. KEY RESULTS: Nebivolol treatment showed significant beneficial effects on subcutaneously transplanted ovaries, as evidenced by improved follicular growth. Treated animals showed a reduced follicular atresia on both the 6th and 22nd day, with an increased number of growing follicles and an increased follicular activation rate after 22 days. Nebivolol promoted neoangiogenesis, as evidenced by an increase in the number of newly formed vessels, without altering blood perfusion. When the ovaries were transplanted to the kidney capsule, nebivolol treatment did not influence follicle growth and survival. CONCLUSIONS: Overall, our findings suggested that nebivolol treatment has promising therapeutic potential to preserve ovarian function and promote neoangiogenesis, particularly in poorly vascularized transplantation sites. IMPLICATIONS: This study has opened new perspectives for the use of pharmacological angiogenic inducers to preserve ovarian integrity and function after transplantation.