Résumés
Résumé
L’étude chromosomique des ovocytes humains issus d’échecs de fécondation in vitro, constitue une approche directe des mécanismes de non-disjonction chromosomique, malgré les difficultés techniques inhérentes à l’analyse de ces cellules. Une étude réalisée sur un vaste échantillon de 1 397 caryotypes ovocytaires a permis de réaliser une analyse fiable et précise de la corrélation existant entre la formation méiotique de ces anomalies et l’âge maternel. Deux modes de non-disjonction méiotique ont été identifiés : la non-disjonction classique de chromosomes entiers et un type particulier de séparation prématurée des chromatides aboutissant à la transmission méiotique de chromatides isolées. Ces deux formes de non-disjonction sont corrélées à l’âge maternel, mais il apparaît que la corrélation est beaucoup plus significative pour le mode de séparation prématurée des chromatides. Ce phénomène constitue donc un mécanisme essentiel de non-disjonction dans le sexe féminin, et pourrait être lié à une perte progressive de la cohésion moléculaire assurée par des protéines spécifiques (les cohésines) entre les chromatides homologues.
Summary
Maternal ageing is the only etiological factor unequivocally associated with the occurrence of aneuploid conceptuses. Molecular studies of trisomies have demonstrated that the pattern of recombinaison was an important predisposing factor to meiotic nondisjunction. To complete this data, a large chromosomal study has been undertaken on 1,397 unfertilised human oocytes recovered from women participating in in vitro fertilization programmes. Conventional whole chromosome nondisjunction and premature chromatid separation were the major types of numerical abnormalities observed. A positive relationship was found between maternal age and these two types of nondisjunction, but the most significant correlation was observed with chromatid separation resulting in the presence of free chromatid in metaphase II oocyte. These data revealed that chromatid separation was an essential factor in the age-dependent occurrence of aneuploidy. This finding provided new insights into the mechanism of nondisjunction in female meiosis since disturbance in molecular chromatid cohesion by cohesins might be a causal mechanism predisposing to nondisjunction and involved in the maternal age effect.
Parties annexes
Références
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