Genetic and pharmacological modulation of Akt1 for improving ovarian graft revascularization in a mouse model

Yoni Cohen, Hagit Dafni, Reut Avni, Liat Fellus, Filip Bochner, Ron Rotkopf, Tal Raz, Laura E. Benjamin, Kenneth Walsh, Michal Neeman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Article number14
JournalBiology of Reproduction
Volume94
Issue number1
DOIs
StatePublished - 1 Jan 2016

Bibliographical note

Publisher Copyright:
© 2016 by the Society for the Study of Reproduction, Inc.

Keywords

  • Akt1
  • Angiogenesis
  • Fertility
  • Ovarian grafts
  • Preservation
  • Simvastatin

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