Jones Keith T
Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Framlington Place, Newcastle, NE2 4HH, UK.
Hum Reprod Update. 2008 Mar-Apr;14(2):143-58. doi: 10.1093/humupd/dmm043. Epub 2007 Dec 14.
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.
哺乳动物的卵母细胞在胎儿卵巢中开始减数分裂，但只有在成年生殖道中受精时才会完成减数分裂。本文综述了这一漫长过程的细胞生物学：从原始生殖细胞进入减数分裂到受孕。减数分裂的决定性特征是连续两次细胞分裂（减数分裂I和II）以及两个细胞周期停滞：在生发泡（GV）期，即减数分裂前期I的双线期，以及在减数分裂中期II。这些停滞被三个关键事件所跨越，这也是本文综述的重点：（i）在胎儿期从有丝分裂过渡到GV停滞，由视黄酸调节；（ii）通过减数分裂I；（iii）受精后完成减数分裂II，这两个减数分裂过程均由细胞周期蛋白依赖性激酶（CDK1）活性调节。人类卵母细胞中的减数分裂I与年龄相关的高染色体错配率有关，如21三体（唐氏综合征），导致非整倍体胚胎。虽然非整倍体可能是多因素造成的，但老年女性的卵母细胞可能由于长期以来将染色体维系在一起的内聚力下降而更容易变成非整倍体。在减数分裂I期间，卵母细胞无法检测到这种损失，要么是因为其对分裂做出反应并阻止分裂的能力也会随着年龄的增长而下降，要么是因为其本身无法对由内聚力丧失引起的分离缺陷类型做出反应。
