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Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

Lookup NU author(s): Professor Mary Herbert, Dimitri Kalleas, Daniel Cooney, Mahdi Lamb, Dr Lisa Lister

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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 mediated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromosomes 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.


Publication metadata

Author(s): Herbert M, Kalleas D, Cooney D, Lamb M, Lister L

Publication type: Review

Publication status: Published

Journal: Cold Spring Harbor Perspectives in Biology

Year: 2015

Volume: 7

Issue: 4

Print publication date: 01/04/2015

ISSN (print): 2157-1422

ISSN (electronic): 1943-0264

URL: http://cshperspectives.cshlp.org/content/7/4/a017970.abstract

DOI: 10.1101/cshperspect.a017970

PubMed id: 25833844


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