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Biol Reprod. 2016 Jan;94(1):14. doi: 10.1095/biolreprod.115.131987. Epub 2015 Oct 21.

Genetic and Pharmacological Modulation of Akt1 for Improving Ovarian Graft Revascularization in a Mouse Model.

Author information

1
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel Racine IVF unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
2
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
3
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
4
Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
5
Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel.
6
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
7
Boston University School of Medicine, Department of Medicine, Boston, Massachusetts.
8
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel Michal.neeman@weizmann.ac.il.

Abstract

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.

KEYWORDS:

Akt1; angiogenesis; fertility; ovarian grafts; preservation; simvastatin

PMID:
26490838
DOI:
10.1095/biolreprod.115.131987
[Indexed for MEDLINE]

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