Eichenlaub-Ritter U
Universität Bielefeld, Fakultät für Biologie, Bielefeld, Germany.
Maturitas. 1998 Oct 12;30(2):143-69. doi: 10.1016/s0378-5122(98)00070-x.
Correlations between parental age, aneuploidy in germ cells and recent findings on aetiological factors in mammalian trisomy formation are reviewed.
Data from observations in human oocytes, molecular studies on the origin of extra chromosomes in trisomies, experiments in a mouse model system, and transgenic approaches are shown.
Errors in chromosome segregation are most frequent in meiosis I of oogenesis in mammals and predominantly predispose specific chromosomes and susceptible chiasmate configurations to maternal age-related nondisjunction. Studies on spindle structure, cell cycle and chromosome behaviour in oocytes of the CBA/Ca mouse used as a model for the maternal age-effect suggest that hormonal homeostasis and size of the follicle pool influence the quality, maturation competence and spindle size of the mammalian oocyte. Predisposition to errors in chromosome segregation are critically dependent on altered cell cycles. Compromised protein synthesis and mitochondrial function affect maturation kinetics and spindle formation, and cause untimely segregation of chromosomes (predivision), mimicking an aged phenotype.
Altered cell cycles and untimely resolution of chiasmata but also nondisjunction of late segregating homologues caused by asynchrony in cytoplasmic and nuclear maturation appear to be causal to errors in chromosome segregation with advanced maternal age. Oocytes appear to lack checkpoints guarding against untimely chromosome segregation. Genes and exposures affecting pool size, hormonal homeostasis and interactions between oocytes and their somatic compartment and thus quality of follicles and oocytes have the potential to critically influence chromosome distribution in female meiosis and affect fertility in humans and other mammals.
综述父母年龄、生殖细胞非整倍体与哺乳动物三体形成病因学因素最新研究结果之间的相关性。
展示了来自人类卵母细胞观察的数据、三体中额外染色体起源的分子研究、小鼠模型系统实验以及转基因方法的相关内容。
染色体分离错误在哺乳动物卵子发生的减数分裂I中最为常见，并且主要使特定染色体和易发生交叉的构型易患与母亲年龄相关的不分离。以CBA/Ca小鼠卵母细胞为模型对母亲年龄效应进行的纺锤体结构、细胞周期和染色体行为研究表明，激素稳态和卵泡池大小会影响哺乳动物卵母细胞的质量、成熟能力和纺锤体大小。染色体分离错误的易感性严重依赖于改变的细胞周期。蛋白质合成和线粒体功能受损会影响成熟动力学和纺锤体形成，并导致染色体过早分离（预分裂），模拟衰老表型。
细胞周期改变、交叉过早解离以及细胞质和细胞核成熟不同步导致的后期分离同源染色体不分离似乎是母亲年龄增长导致染色体分离错误的原因。卵母细胞似乎缺乏防止染色体过早分离的检查点。影响卵泡池大小、激素稳态以及卵母细胞与其体细胞成分之间相互作用从而影响卵泡和卵母细胞质量的基因和暴露因素，有可能严重影响女性减数分裂中的染色体分布，并影响人类和其他哺乳动物的生育能力。
