title: Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age.
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.
authors: Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Framlington Place, Newcastle, NE2 4HH, UK. k.t.jones@ncl.ac.uk
authors: Keith T
authors: KT
authors: Jones
mesh_terms: D000367:Age Factors; D000782:Aneuploidy; D000818:Animals; D005260:Female; D005306:Fertilization; D006801:Humans; D015994:Incidence; D008540:Meiosis; D008938:Mitosis; D009865:Oocytes / Q000166:cytology* / Q000502:physiology*