title: Influence of p53 and genetic background on prenatal oogenesis and oocyte attrition in mice.
abstract: BACKGROUND
  Meiotic progression, and the number of oocytes surviving to birth, determine the ovarian reserve, yet the control of prenatal oogenesis is poorly understood. We investigated the effects of genetic background and p53 upon oogenesis in mice.
  
  
  METHODS
  Fetal and neonatal ovaries were analysed in B6CBf1 and B6CBf2 mice from 15.5 to 21 days post-coitum (dpc) and p53 (a tumour suppressor gene) knockout, heterozygous and wild-type mice from 15.5 to 16 dpc. Oocytes in meiotic prophase I (MPI) were identified by labelling synaptonemal complex protein 3, and the specific stage of MPI was classified by the appearance of axial elements. Apoptosis and DNA breaks were assessed by cleaved poly-(ADP-ribose) polymerase (PARP-1) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL), respectively.
  
  
  RESULTS
  The leptotene, zygotene and pachytene stages were earlier in f1 than f2 generations with significant differences at all stages (P< or =0.002). The p53(-/-) oocyte populations and those with the presence of p53 gene differed significantly in terms of: (i) the proportion of oocytes reaching specific stages of MPI on 15.5 and 16 dpc and (ii) the proportion of oocytes having observed abnormalities in synaptonemal complexes (P < 0.001). The absence of p53 resulted in faster progression of oocytes and more with compressed and abnormal axial elements. We observed significant differences between p53(-/-), p53(+/-) and p53(+/+) mice in terms of cleaved PARP-1 staining and TUNEL.
  
  
  CONCLUSIONS
  Genotype has an important impact on prenatal meiosis and oocyte apoptosis. p53 affects the speed of oocyte development and may influence the oocyte selection through apoptosis during MPI.
authors.affiliation: Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK.
authors.forename: F
authors.initials: F
authors.lastname: Ghafari
authors.forename: S
authors.initials: S
authors.lastname: Pelengaris
authors.forename: E
authors.initials: E
authors.lastname: Walters
authors.forename: G M
authors.initials: GM
authors.lastname: Hartshorne
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020287:In Situ Nick-End Labeling; D008297:Male; D049469:Meiotic Prophase I / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000502:physiology*; D009866:Oogenesis / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011247:Pregnancy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C490062:Sycp3 protein, mouse; D016159:Tumor Suppressor Protein p53; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases