In search of signaling pathways critical for ovarian graft reception: Akt1 is essential for long-term survival of ovarian grafts

Objective To explore the role of Akt1, a principle modulator of angiogenesis, in ovarian graft reception and to investigate whether Akt1 deficiency can alter ovarian graft reception. Design Experimental mouse model. Setting Research institute. Animal(s) Donors: Akt1 knockout (Akt1^-/-) and wild types (Akt1^+/+) mice. Recipients: CD-1 nude immune deficient female mice. Intervention(s) Ovaries from Akt1^-/- and Akt1^+/+ mice transplanted in the biceps femoris muscle of immunocompromised CD-1 mice, and ovarian graft viability, perfusion, and revascularization explored in vivo by magnetic resonance imaging (MRI). Main Outcome Measure(s) Vascular density and permeability of newly formed graft blood vessels quantified by dynamic contrast-enhanced MRI 7, 14, 30, and 60 days after grafting as indicators for angiogenesis and reestablishment of blood perfusion. Result(s) The Akt1^-/- ovarian grafts showed a gradual decrease in angiogenic response with time after transplantation, ultimately leading to complete or near-complete graft destruction coinciding with massive follicular loss. Sixty days after transplantation, the mean blood volume fraction (fBV) and vessel permeability (PS) were statistically significantly lower in Akt1^-/- transplants compared with Akt1^+/+. Conclusion(s) Akt1 is essential for ovarian graft reception. However, surprisingly the impact of Akt1 deficiency was most profound not in the early stages of angiogenesis but rather in long-term survival of the graft.