title: Increased number of multi-oocyte follicles (MOFs) in juvenile p27Kip1 mutant mice: potential role of granulosa cells.
abstract: OBJECTIVE
  Why are female mice that lack a functional p27 protein infertile?
  
  
  CONCLUSIONS
  The absence of a functional p27 leads to a dramatic increase in the number of multi-oocyte follicles (MOFs) in juvenile female mice; p27 would promote the individualization of follicles favoring the development of fertile eggs.
  
  
  BACKGROUND
  p27-/- female mice are infertile. p27 suppresses excessive follicular endowment and activation and promotes follicular atresia in mice.
  
  
  METHODS
  Ovaries from wild type (WT) and p27Kip1 mutant mice aged 2, 4 and 12 weeks were subjected to immunohistochemistry/immunofluorescence. The slides with whole organs serially sectioned were scanned and examined by image analysis.
  
  
  RESULTS
  Compared with WT, p27Kip1 mutant pre-pubertal mice had a greater number of oocytes, a greater number of growing follicles and a greater number of MOFs. These differences were statistically significant (P < 0.05), particularly in the case of MOFs (P > 0.001). The unusually large number of MOFs in juvenile p27-deficient mice is a novel observation. In WT mice p27 protein remains present in the oocyte nucleus but gradually decreases in the ooplasm during follicular growth, while granulosa cells show dynamic, follicle stage-related changes.
  
  
  CONCLUSIONS
  These results have been obtained in mice and they cannot be directly extrapolated to humans.
  
  
  CONCLUSIONS
  The dramatic increase in the numbers of MOFs in juvenile p27 mutants has not been previously reported. The number of MOFs declines sharply as the mice become sexually mature, pointing to their negative selection. These findings open a new approach to the study of sterility.
  
  
  BACKGROUND
  This study has been funded by the Basque Government, Dept. of Health grant 2007111063 and Dept. of Industry (Saiotek) grant S-PC11UN008. Jairo Perez-Sanz was the recipient of a grant from Fundación Jesús de Gangoiti Barrera. The authors have no conflicts of interest to declare.
authors.affiliation: Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, 48940 Leioa-Bizkaia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pérez-Sanz
authors.forename: J
authors.initials: J
authors.lastname: Arluzea
authors.forename: R
authors.initials: R
authors.lastname: Matorras
authors.forename: N
authors.initials: N
authors.lastname: González-Santiago
authors.forename: J
authors.initials: J
authors.lastname: Bilbao
authors.forename: N
authors.initials: N
authors.lastname: Yeh
authors.forename: A
authors.initials: A
authors.lastname: Barlas
authors.forename: Y
authors.initials: Y
authors.lastname: Romin
authors.forename: K
authors.initials: K
authors.lastname: Manova-Todorova
authors.forename: A
authors.initials: A
authors.lastname: Koff
authors.forename: C
authors.initials: C
authors.lastname: de la Hoz
mesh_terms: D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis / Q000235:genetics*; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D007150:Immunohistochemistry; D007246:Infertility / Q000235:genetics; D051379:Mice; D009154:Mutation; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D012741:Sexual Maturation
chemical_list: C493961:Cdkn1b protein, mouse; D050760:Cyclin-Dependent Kinase Inhibitor p27