title: Short-Term PTEN Inhibition Improves In Vitro Activation of Primordial Follicles, Preserves Follicular Viability, and Restores AMH Levels in Cryopreserved Ovarian Tissue From Cancer Patients.
abstract: BACKGROUND
  In vitro activation and growth of primordial dormant follicles to produce fertilizable oocytes would provide a useful instrument for fertility preservation. The employment of Phosphatase and TENsin homolog (PTEN) inhibitors, in combination with Protein kinase B (Akt) stimulating molecules, has been previously employed to increase follicular activation through the stimulation of the PTEN-Akt pathway.
  
  
  METHODS
  We aim to establish improved in vitro activation also for cancer patients whose ovarian tissue has already been cryopreserved. Fresh and previously cryopreserved human ovarian cortex were exposed to short-term, low-concentration and ovary-specific treatment with only a PTEN inhibitor.
  
  
  RESULTS
  Our in vitro activation protocol enhances the activation mechanisms of primordial follicles in both fresh and cryopreserved samples, and enlarges growing populations without inducing apoptosis in either follicles or the surrounding stroma. Treatment augments estradiol secretion and restores the expression levels of the previously diminished Anti-Müllerian hormone by means of cryopreservation procedures. Genomic modulation of the relative expression of PTEN pathway genes was found in treated samples.
  
  
  CONCLUSIONS
  The in vitro activation protocol offers new alternatives for patients with cryopreserved tissue as it increases the pool of viable activated follicles available for in vitro growth procedures. The combination of ovarian tissue cryopreservation and in vitro activation of primordial follicles, the main ovarian reserve component, will be a major advancement in fertility preservation.
authors.affiliation: Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Grupo de investigación de Medicina Reproductiva. Instituto de Investigación Sanitario La Fe. Valencia, Spain; Unidad de Preservación de la Fertilidad, Área de Salud de la Mujer. Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Novella-Maestre
authors.affiliation: Grupo de investigación de Medicina Reproductiva. Instituto de Investigación Sanitario La Fe. Valencia, Spain; Unidad de Preservación de la Fertilidad, Área de Salud de la Mujer. Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Herraiz
authors.affiliation: Grupo de investigación de Medicina Reproductiva. Instituto de Investigación Sanitario La Fe. Valencia, Spain; Unidad de Preservación de la Fertilidad, Área de Salud de la Mujer. Hospital Universitario y Politécnico La Fe, Valencia, Spain; IGENOMIX, Parc Cientific Valencia University, Paterna, Valencia, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rodríguez-Iglesias
authors.affiliation: Grupo de investigación de Medicina Reproductiva. Instituto de Investigación Sanitario La Fe. Valencia, Spain; Unidad de Preservación de la Fertilidad, Área de Salud de la Mujer. Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Díaz-García
authors.affiliation: Grupo de investigación de Medicina Reproductiva. Instituto de Investigación Sanitario La Fe. Valencia, Spain; Unidad de Preservación de la Fertilidad, Área de Salud de la Mujer. Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D054304:Anti-Mullerian Hormone / Q000096:biosynthesis*; D015925:Cryopreservation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009369:Neoplasms; D009926:Organ Preservation; D006080:Ovarian Follicle / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014022:Tissue Survival
chemical_list: D004791:Enzyme Inhibitors; D054304:Anti-Mullerian Hormone; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human