Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes

Hum Genet. 2003 Feb;112(2):195-203. doi: 10.1007/s00439-002-0852-x. Epub 2002 Oct 29.

Abstract

The effect of maternal age on the incidence of chromosomal abnormalities was investigated on a large sample of 3,042 in vitro unfertilized human oocytes II obtained from 792 women aged 19-46 years and participating in an in vitro fertilization program for various indications. The chromosomal analysis combined a gradual fixation of oocytes and an adapted R-banding technique. A total of 1,397 interpretable karyotypes were obtained. Various types of numerical aberration were observed, involving conventional chromosome nondisjunction (3.5%), single-chromatid nondisjunction (5.9%), complex (0.8%) or extreme aneuploidy (0.5%), diploidy (5.4%), and set of single chromatids (3.8%). No significant difference was found in the mean age of women according to the various types of chromosomal abnormalities. A positive relationship was found between maternal age and the global rate of aneuploidy, in agreement with the findings of epidemiological studies. The incidence of both whole-chromosome nondisjunction and precocious chromatid separation were correlated to maternal aging but the most significant correlation was found between maternal aging and single-chromatid nondisjunction. The rate of diploidy was also correlated to a slight extent to maternal aging, whereas no correlation was found between maternal age and the rate of single-chromatid sets. These data reveal that single-chromatid malsegregation is an essential factor in the age-dependent occurrence of nondisjunction in human oocytes. Disturbance in sister-chromatid cohesion might be a causal mechanism predisposing to premature chromatid separation and subsequently to nondisjunction in female meiosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aneuploidy
  • Chromatids / physiology
  • Chromosome Segregation
  • Chromosomes, Human, X
  • Diploidy
  • Female
  • Fertilization in Vitro
  • Haploidy
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infertility, Female / genetics
  • Infertility, Female / pathology
  • Karyotyping
  • Maternal Age*
  • Meiosis / physiology*
  • Middle Aged
  • Nondisjunction, Genetic*
  • Oocytes / physiology*
  • Polyploidy
  • Pregnancy