Meiosis and maternal aging: Insights from aneuploid oocytes and trisomy births

Mary Herbert, Dimitrios Kalleas, Daniel Cooney, Mahdi Lamb, Lisa Lister

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149 Citations (Scopus)

Abstract

In most organisms, genome haploidization requires reciprocal DNA exchanges (crossovers) between replicated parental homologs to form bivalent chromosomes. These are resolved to their four constituent chromatids during two meiotic divisions. In female mammals, bivalents are formed during fetal life and remain intact until shortly before ovulation. Extending this period beyond ~35 years greatly increases the risk of aneuploidy in human oocytes, resulting in a dramatic increase in infertility, miscarriage, and birth defects, most notably trisomy 21. Bivalent chromosomes are stabilized by cohesion between sister chromatids, which is me-diated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromo-somes during female aging. Consistent with this, premature loss of centromeric cohesion is a major source of aneuploidy in oocytes from older women. Here, we propose a mechanistic framework to reconcile data from genetic studies on human trisomy and oocytes with recent advances in our understanding of the molecular mechanisms of chromosome segregation during meiosis in model organisms.

Original languageEnglish
Article numbera017970
Number of pages22
JournalCold Spring Harbor Perspectives in Biology
Volume7
Issue number4
DOIs
Publication statusPublished - 2015
Externally publishedYes

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