Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes.
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.
Pellestor
Franck
F
CNRS-UPR1142, 141 Rue de la Cardonille, 34396 Montpellier cedex 5, France. Franck.Pellestor@igh.cnrs.fr
Andréo
Brigitte
B
Arnal
Françoise
F
Humeau
Claude
C
Demaille
Jacques
J
D000328:Adult; D000782:Aneuploidy; D002842:Chromatids / Q000502:physiology; D020090:Chromosome Segregation; D041321:Chromosomes, Human, X; D004171:Diploidy; D005260:Female; D005307:Fertilization in Vitro; D006238:Haploidy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007247:Infertility, Female / Q000235:genetics / Q000473:pathology; D007621:Karyotyping; D008423:Maternal Age; D008540:Meiosis / Q000502:physiology*; D008875:Middle Aged; D009630:Nondisjunction, Genetic; D009865:Oocytes / Q000502:physiology*; D011123:Polyploidy; D011247:Pregnancy