title: Experimental evidence that changes in oocyte growth influence meiotic chromosome segregation.
abstract: BACKGROUND
  It is well known that the fidelity of meiotic chromosome segregation is greatly reduced with increasing maternal age in humans. More recently, direct studies of human oocytes have demonstrated a striking age-related increase in oocytes exhibiting gross disturbances in chromosome alignment on the meiotic spindle. This abnormality, termed congression failure, has been postulated to be causally related to human non-disjunction and to result from subtle alterations in folliculogenesis that develop with advancing reproductive age.
  
  
  METHODS
  Immunofluorescence staining, conventional cytogenetic analysis and spectral karyotyping of oocytes from mouse models were used to investigate the hypothesis that changes in the regulation of folliculogenesis induce meiotic defects.
  
  
  RESULTS
  Mutations that affect oocyte growth were found to increase the frequency of congression failure at first meiotic metaphase. Importantly, increased congression failure was correlated with meiotic non-disjunction, suggesting a cause-and-effect relationship.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that congression failure results from disturbances in the complex interplay of signals regulating folliculogenesis and that these changes subtly alter the late stages of oocyte growth, increasing the risk of a non-disjunction error. These findings have important implications for human aneuploidy, since they suggest that it may be possible to develop prophylactic treatments for reducing the risk of age-related aneuploidy.
authors: Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106-4955, USA.
authors: C A
authors: CA
authors: Hodges
authors: A
authors: A
authors: Ilagan
authors: D
authors: D
authors: Jennings
authors: R
authors: R
authors: Keri
authors: J
authors: J
authors: Nilson
authors: P A
authors: PA
authors: Hunt
mesh_terms: D000705:Anaphase; D000782:Aneuploidy; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D005260:Female; D008297:Male; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000166:cytology* / Q000502:physiology; D006080:Ovarian Follicle / Q000502:physiology