title: In search of signaling pathways critical for ovarian graft reception: Akt1 is essential for long-term survival of ovarian grafts.
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.
  
  
  METHODS
  Experimental mouse model.
  
  
  METHODS
  Research institute.
  
  
  METHODS
  Donors: Akt1 knockout (Akt1(-/-)) and wild types (Akt1(+/+)) mice. Recipients: CD-1 nude immune deficient female mice.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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(+/+).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yoni
authors.initials: Y
authors.lastname: Cohen
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Dafni
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Reut
authors.initials: R
authors.lastname: Avni
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel; Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Raz
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Biton
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Brian
authors.initials: B
authors.lastname: Hemmings
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel. Electronic address: michal.neeman@weizmann.ac.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
mesh_terms: D000818:Animals; D005260:Female; D006085:Graft Survival / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D010053:Ovary / Q000098:blood supply / Q000378:metabolism* / Q000637:transplantation*; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
chemical_list: C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt1; MRI; angiogenesis; fertility preservation; ovarian graft