Center for Reproductive Medicine, Shandong University, Jinan, Shandong, 250012, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.
Bioessays. 2019 Oct;41(10):e1800221. doi: 10.1002/bies.201800221. Epub 2019 Aug 19.
A striking feature of human female sexual reproduction is the high level of gametes that exhibit an aberrant number of chromosomes (aneuploidy). A high baseline observed in women of prime reproductive age is followed by a dramatic increase in older women. Proper chromosome segregation requires one or more DNA crossovers (COs) between homologous maternal and paternal chromosomes, in combination with cohesion between sister chromatid arms. In human females, CO designations occur normally, according to the dictates of CO interference, giving early CO-fated intermediates. However, ≈25% of these intermediates fail to mature to final CO products. This effect explains the high baseline of aneuploidy and is predicted to synergize with age-dependent cohesion loss to explain the maternal age effect. Here, modern advances in the understanding of crossing over and CO interference are reviewed, the implications of human female CO maturation inefficiency are further discussed, and areas of interest for future studies are suggested.
人类女性生殖的一个显著特征是大量配子表现出异常数量的染色体（非整倍体）。在处于最佳生育年龄的女性中观察到的高基线水平，随后在老年女性中急剧增加。正确的染色体分离需要一个或多个同源母本和父本染色体之间的 DNA 交叉（CO），以及姐妹染色单体臂之间的凝聚力。在人类女性中，CO 的指定通常根据 CO 干扰的要求发生，从而产生早期的 CO 注定中间体。然而，这些中间体中有 ≈25%未能成熟为最终的 CO 产物。这种效应解释了非整倍体的高基线，并预计与年龄相关的凝聚力丧失协同作用，以解释母体年龄效应。在这里，综述了对交叉和 CO 干扰的理解的现代进展，进一步讨论了人类女性 CO 成熟效率低下的影响，并提出了未来研究的兴趣领域。
