Genetic and Pharmacological Modulation of Akt1 for Improving Ovarian Graft Revascularization in a Mouse Model.
Ovarian tissue cryopreservation and transplantation is one of a few available treatments for fertility preservation in women diagnosed with cancer. Rapid revascularization is essential for reducing hypoxic damage after grafting and protecting the primordial follicles reserve. Using a mouse model of heterotopic ovarian graft transplantation, we have delineated the role of endothelial Akt1 expression using longitudinal magnetic resonance imaging follow-up to quantify angiogenic response. Endothelial Akt1 activation in ovarian grafts promoted angiogenesis to support the graft during posttransplantation hypoxic period. Similarly, simvastatin therapy activated Akt1 at the transplantation site and improved the revascularization and vascular support of ovarian grafts. These results serve as an important first step toward pharmacological intervention to improve revascularization of ovarian grafts and restoration of fertility in cancer survivors. The pro-angiogenic effects reported here may extend beyond improving ovarian graft reception in fertility preservation and could potentially be used for different organ or tissue transplantation.
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel Racine IVF unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Yoni
Y
Cohen
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
Hagit
H
Dafni
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Reut
R
Avni
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Liat
L
Fellus
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
Filip
F
Bochner
Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
Ron
R
Rotkopf
Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel.
Tal
T
Raz
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Laura E
LE
Benjamin
Boston University School of Medicine, Department of Medicine, Boston, Massachusetts.
Kenneth
K
Walsh
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel Michal.neeman@weizmann.ac.il.
Michal
M
Neeman
D000818:Animals; D015925:Cryopreservation; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism; D007247:Infertility, Female / Q000628:therapy; D008279:Magnetic Resonance Imaging; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics*; D006080:Ovarian Follicle / Q000187:drug effects; D010053:Ovary / Q000098:blood supply* / Q000637:transplantation*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D012039:Regional Blood Flow; D019821:Simvastatin / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
Akt1; angiogenesis; fertility; ovarian grafts; preservation; simvastatin