title: Primordial follicle activation in the ovary of Ames dwarf mice.
abstract: BACKGROUND
  The insulin receptor substrate 1 (IRS1), phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt1), Forkhead Box O3a (FOXO3a) pathway is directly involved in aging and ovarian activation of follicle growth. Therefore, the aim of this work was to measure the expression of genes related to the ovarian pathway for activation of primordial follicles and FOXO3a protein phosphorylation between young and old female Ames dwarf (df/df) and normal (N) mice.
  
  
  METHODS
  For this study ovaries from N (n = 10) and df/df (n = 10) female mice were collected at 5-6 months of age and at 21-22 months of age. For immunohistochemistry ovaries from 12 month-old and df/df mice were used.
  
  
  RESULTS
  The expression of Irs1, Pi3k, Akt1, mammalian target of rapamycin (Mtor), suppressor of cytokine signaling -2 (Socs2), Socs3 was lower (P < 0.05) in older than younger N mice and not different (P > 0.05) between young and old df/df mice. The expression of Foxo3a was also lower (P < 0.05) in old than younger N and df/df mice and was higher (P < 0.05) in old df/df than N mice. Expression of Amh was lower (P < 0.05) in old than young N and df/df mice and was higher (P = 0.0009) in df/df than N mice. Imunnostaining for p-FOXO3 was lower in df/df than N mice (P < 0.001), although FOXO3 immunostaining was not different (P > 0.05) between df/df and N mice.
  
  
  CONCLUSIONS
  In sum, the present study indicates that lower expression of Irs1, Socs2, Socs3, Akt1, Pi3k, Mtor and Foxo3a mRNA in the ovaries of older mice of both genotypes is associated to a reduced ovarian activity revealed by lower expression of Amh mRNA. At the same time, ovaries of old df/df mice maintained higher expression of Foxo3a mRNA, which was associated to higher ovarian activity. We have shown that df/df females have a lower level of p-FOXO3 in oocytes from primordial/primary follicles, an important activator of follicular growth. Therefore, this study strongly indicates that Prop1(df) mutation causes delayed ovarian aging.
authors.affiliation: Faculdade de Nutrição, Universidade Federal de Pelotas, Rua Gomes Carneiro, 1 Sala 239, CEP 96020-220, Pelotas, RS, Brazil. augusto.schneider@ufpel.edu.br.
authors.forename: Augusto
authors.initials: A
authors.lastname: Schneider
authors.affiliation: College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA. zhixujp@hotmail.com.|Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China. zhixujp@hotmail.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhi
authors.affiliation: Faculdade de Veterinária, Universidade Federal de Pelotas, Pelotas, RS, Brazil. fabimorvet@gmail.com.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Moreira
authors.affiliation: Faculdade de Veterinária, Universidade Federal de Pelotas, Pelotas, RS, Brazil. tluciajr@gmail.com.
authors.forename: Thomaz
authors.initials: T
authors.lastname: Lucia
authors.affiliation: Instituto de Biologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil. rgmondadori@gmail.com.
authors.forename: Rafael Gianella
authors.initials: RG
authors.lastname: Mondadori
authors.affiliation: College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA. michal.masternak@ucf.edu.|Department of Head and Neck Surgery, The Greater Poland Cancer Centre, 15 Garbary St., 61-866, Poznan, Poland. michal.masternak@ucf.edu.
authors.forename: Michal M
authors.initials: MM
authors.lastname: Masternak
mesh_terms: D000818:Animals; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D006080:Ovarian Follicle / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism
chemical_list: D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt