Human Reproduction Update Advance Access originally published online on December 14, 2007
Human Reproduction Update 2008 14(2):143-158; doi:10.1093/humupd/dmm043
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Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age
Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Framlington Place, Newcastle, NE2 4HH, UK
1 Correspondence address. Tel: +44-191-222-6963; Fax: +44-191-222-7424; k.t.jones{at}ncl.ac.uk
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.
Key words: aneuploidy / fertilization / meiosis / cocyte
Received on September 18, 2007; revised October 19, 2007; accepted on November 2, 2007
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