Molecular basis of maternal age-related increase in oocyte aneuploidy
Molecular basis of maternal age-related increase in oocyte aneuploidy
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DOI：
10.1111/j.1741-4520.2011.00350.x
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发表时间：
2012-03-01
影响因子：
1.3
通讯作者：
Ohye, Tamae
中科院分区：
文献类型：
--
作者：
Kurahashi, Hiroki;Tsutsumi, Makiko;Ohye, Tamae
非整倍体是人类最常见和最严重的妊娠并发症之一。大多数患有常染色体非整倍体的孕妇在子宫内死亡，导致早期妊娠流产。然而，一些非整倍体的胎儿存活到足月，但患有与先天性异常和智力迟钝相关的疾病，如唐氏综合症与21三体。这种情况的三个一般特征是公认的：(i)在大多数情况下，额外的染色体是母系起源；（ii）大多数病例源于减数分裂I中的分离不良事件；（三）这些错误的发生频率随着母亲年龄的增长而增加。减数分裂I型错误的年龄依赖性增加的基础一直是一个长期的谜。许多研究人员通过对额外的21号染色体进行基因组分析，利用多态标记来确定交叉的频率或位置，从而解决了这种生物学现象的本质，从而确保了染色体的忠实分离。体外未受精卵母细胞的细胞遗传学分析也已进行。然而，这些研究尚未得出关于减数分裂I型错误的明确结论。最近在条件敲除小鼠减数分裂特异性粘接蛋白的研究结果进一步阐明了这一问题。本文综述了目前对年龄相关非整倍体的认识，并概述了相关机制。我们引用最近的数据来说明这个领域中出现的一些新范式。
Aneuploidy is one of the most common and serious pregnancy complications in humans. Most conceptuses with autosomal aneuploidy die in utero, resulting in early pregnancy loss. However, some fetuses with aneuploidy survive to term but suffer from disorders associated with congenital anomalies and mental retardation, such as Down syndrome with trisomy 21. Three general characteristics of this condition are well acknowledged: (i) in most cases the extra chromosome is of maternal origin; (ii) most cases are derived from a malsegregation event in meiosis I; and (iii) the frequency of these errors increases with maternal age. The basis for the age-dependent increase in meiosis I errors has been a long-standing enigma. Many investigators have addressed the nature of this biological phenomenon through genomic analyses of extra chromosome 21 using polymorphic markers to determine the frequency or location of crossovers that should ensure faithful chromosome segregation. Cytogenetic analyses of in vitro unfertilized oocytes have also been performed. However, no definitive conclusions regarding meiosis I errors have yet been reached from such studies. Recent findings in conditional knock-out mice for meiosis-specific cohesin have shed further light on this issue. The present review focuses on the current understanding of age-related aneuploidy and provides an overview of the mechanisms involved. We refer to recent data to illustrate some of the new paradigms that have arisen in this field.