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 singlechromatid 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 singlechromatid malsegregation is an essential factor in the agedependent 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.

The implication of both chromosome and chromatid abnormalities in the occurrence of non-disjunction are discussed in relation to the recent data on chromatid cohesion throughout cell division. The results were consistent with the hypothesis of an unequal occurrence of non-disjunction among the chromosome groups in female meiosis.

No abstract

The possibility that a chromosomal rearrangement might disturb the meiotic behaviour of chromosomes not involved in the rearrangement and favour non-disjunction is a controversial issue in human cytogenetics. Using two-colour fluorescence in-situ hybridization and primed in-situ labelling techniques, we have investigated the segregation pattern of 10 chromosomes (chromosomes 1, 4, 9, 13, 15, 16, 20, 21, X and Y) in spermatozoa from nine carriers of balanced structural rearrangements and three normal men. The patients were divided into two groups according to their semen parameters. In rearrangement carriers and normal subjects, sex chromosomes and chromosome 21 displayed a higher rate of disomy than the other chromosomes. No evidence for the occurrence of interchromosomal effect was found in the spermatozoa of fertile rearrangement carriers, but significant variations were observed for all chromosomes tested in the group of infertile translocation carriers, suggesting a direct correlation between poor quality spermatozoa and increased aneuploidy rate in this group. In fertile carriers of chromosomal rearrangements, the occurrence of non-disjunction of chromosomes not involved in the rearrangement might therefore be considered as fortuitous, whereas in infertile carriers, the risk for interchromosomal effect appears to be real and should be taken into consideration in the genetic counselling of infertile couples with a male partner carrying a chromosomal rearrangement.