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

Citation:

Yoni Cohen, Dafni, Hagit , Avni, Reut , Raz, Tal , Biton, Inbal , Hemmings, Brian , and Neeman, Michal . 2014. “In Search Of Signaling Pathways Critical For Ovarian Graft Reception: Akt1 Is Essential For Long-Term Survival Of Ovarian Grafts”. Fertil Steril, 101, 2, Pp. 536-44. doi:10.1016/j.fertnstert.2013.10.007.

Abstract:

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.