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Meiosis in oocytes: Predisposition to aneuploidy and its increased incidence with age

Lookup NU author(s): Professor Keith Jones

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Abstract

Mammalian oocytes begin meiosis in the fetal ovary, but only complete it when fertilized in the adult reproductive tract. This review examines the cell biology of this protracted process: from entry of primordial germ cells into meiosis to conception. The defining feature of meiosis is two consecutive cell divisions (meiosis I and II) and two cell cycle arrests: at the germinal vesicle (GV), dictyate stage of prophase I and at metaphase II. These arrests are spanned by three key events, the focus of this review: (i) passage from mitosis to GV arrest during fetal life, regulated by retinoic acid; (ii) passage through meiosis I and (iii) completion of meiosis II following fertilization, both meiotic divisions being regulated by cyclin-dependent kinase (CDK1) activity. Meiosis I in human oocytes is associated with an age-related high rate of chromosomal mis-segregation, such as trisomy 21 (Down's syndrome), resulting in aneuploid conceptuses. Although aneuploidy is likely to be multifactorial, oocytes from older women may be predisposed to be becoming aneuploid as a consequence of an age-long decline in the cohesive ties holding chromosomes together. Such loss goes undetected by the oocyte during meiosis I either because its ability to respond and block division also deteriorates with age, or as a consequence of being inherently unable to respond to the types of segregation defects induced by cohesion loss. © The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Publication metadata

Author(s): Jones KT

Publication type: Review

Publication status: Published

Journal: Human Reproduction Update

Year: 2008

Volume: 14

Issue: 2

Pages: 143-158

Print publication date: 01/03/2008

ISSN (print): 1355-4786

ISSN (electronic): 1460-2369

URL: http://dx.doi.org/10.1093/humupd/dmm043

DOI: 10.1093/humupd/dmm043

PubMed id: 18084010


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