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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cryopreservation
  • Female
  • Graft Survival / drug effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hypoxia / metabolism
  • Infertility, Female / therapy
  • Magnetic Resonance Imaging
  • Mice
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics*
  • Ovarian Follicle / drug effects
  • Ovary / blood supply*
  • Ovary / transplantation*
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / genetics*
  • Regional Blood Flow
  • Simvastatin / pharmacology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt