Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, China.
Asian J Androl. 2021 Nov-Dec;23(6):562-571. doi: 10.4103/aja.aja_86_20.
Repairing DNA double-strand breaks (DSBs) with homologous chromosomes as templates is the hallmark of meiosis. The critical outcome of meiotic homologous recombination is crossovers, which ensure faithful chromosome segregation and promote genetic diversity of progenies. Crossover patterns are tightly controlled and exhibit three characteristics: obligatory crossover, crossover interference, and crossover homeostasis. Aberrant crossover patterns are the leading cause of infertility, miscarriage, and congenital disease. Crossover recombination occurs in the context of meiotic chromosomes, and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally. Meiotic chromosomes are organized in a loop-axis architecture. Diverse evidence shows that chromosome axis length determines crossover frequency. Interestingly, short chromosomes show different crossover patterns compared to long chromosomes. A high frequency of human embryos are aneuploid, primarily derived from female meiosis errors. Dramatically increased aneuploidy in older women is the well-known "maternal age effect." However, a high frequency of aneuploidy also occurs in young women, derived from crossover maturation inefficiency in human females. In addition, frequency of human aneuploidy also shows other age-dependent alterations. Here, current advances in the understanding of these issues are reviewed, regulation of crossover patterns by meiotic chromosomes are discussed, and issues that remain to be investigated are suggested.
以同源染色体作为模板修复 DNA 双链断裂 (DSBs) 是减数分裂的标志。减数分裂同源重组的关键结果是交叉,它确保了染色体的正确分离,并促进了后代的遗传多样性。交叉模式受到严格控制,表现出三个特征:强制性交叉、交叉干扰和交叉稳态。异常的交叉模式是不孕、流产和先天性疾病的主要原因。交叉重组发生在减数分裂染色体的背景下,它与减数分裂染色体结构紧密结合,并在局部和全局水平上受到调节。减数分裂染色体以环轴结构组织。多种证据表明,染色体轴长决定了交叉频率。有趣的是,短染色体与长染色体相比表现出不同的交叉模式。人类胚胎的非整倍体率很高,主要来源于女性减数分裂错误。高龄女性中明显增加的非整倍体是众所周知的“母体年龄效应”。然而,在年轻女性中也会出现高频率的非整倍体,这源于人类女性中交叉成熟效率低下。此外,人类非整倍体的频率也表现出其他与年龄相关的变化。在这里,我们综述了对这些问题的理解的最新进展,讨论了减数分裂染色体对交叉模式的调节,并提出了仍需研究的问题。