title: Influence of follicular fluid meiosis-activating sterol on aneuploidy rate and precocious chromatid segregation in aged mouse oocytes.
abstract: BACKGROUND
  Follicular fluid meiosis-activating sterol (FF-MAS) protects young oocytes from precocious chromatid separation (predivision). Reduced expression of cohesion and checkpoint proteins and predivision has been hypothesized to occur in age-related aneuploidy in oocytes.
  
  
  METHODS
  To know whether FF-MAS also protects aged oocytes from predivision and from age-related non-disjunction, we analysed chromosome constitution in mouse oocytes matured spontaneously with or without 10 microM FF-MAS and in hypoxanthine (HX)-arrested young and aged oocytes induced to resume maturation by FF-MAS. Messenger RNA for checkpoint protein MAD2 and cohesion protein SMC1beta was compared between oocytes matured with or without FF-MAS.
  
  
  RESULTS
  Aged oocytes possessed many bivalents with single distal chiasma at meiosis I. Predivision was especially high in aged oocytes cultured sub-optimally to metaphase II in alpha-minimum essential medium (alpha-MEM). FF-MAS reduced predivision significantly (P < 0.001) but neither reduced non-disjunction nor induced aneuploidy in aged oocytes. Polyploidy was high in FF-MAS-stimulated maturation, in particular in the aged oocytes (P > 0.001). Relative levels of Smc1beta mRNA appeared increased by maturation in FF-MAS, and mitochondrial clustering was restored.
  
  
  CONCLUSIONS
  Sister chromatids of aged oocytes appear to be highly susceptible to precocious chromatid separation, especially when maturation is under sub-optimal conditions, e.g. in the absence of cumulus and FF-MAS. This may relate to some loss of chromatid cohesion during ageing. FF-MAS protects aged oocytes from predivision during maturation, possibly by supporting Smc1beta expression, thus reducing risks of meiotic errors, but it cannot prevent age-related non-disjunction. Aged oocytes appear prone to loss of co-ordination between nuclear maturation and cytokinesis suggesting age-related relaxed cell cycle control.
authors.affiliation: Research Laboratories of Schering AG, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Cukurcam
authors.forename: I
authors.initials: I
authors.lastname: Betzendahl
authors.forename: G
authors.initials: G
authors.lastname: Michel
authors.forename: E
authors.initials: E
authors.lastname: Vogt
authors.forename: C
authors.initials: C
authors.lastname: Hegele-Hartung
authors.forename: B
authors.initials: B
authors.lastname: Lindenthal
authors.forename: U
authors.initials: U
authors.lastname: Eichenlaub-Ritter
mesh_terms: D000375:Aging; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D016922:Cellular Senescence; D002782:Cholestenes / Q000494:pharmacology*; D002842:Chromatids / Q000502:physiology*; D020090:Chromosome Segregation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D019271:Hypoxanthine / Q000494:pharmacology; D064246:Mad2 Proteins; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D008808:Mice, Inbred CBA; D009865:Oocytes / Q000502:physiology*; D009930:Organic Chemicals; D011123:Polyploidy
chemical_list: D018797:Cell Cycle Proteins; D002782:Cholestenes; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; D009930:Organic Chemicals; C438001:Smc1l2 protein, mouse; C420642:alpha minimal essential medium; D019271:Hypoxanthine; C100324:4,4-dimethylcholesta-8,14,24-trienol