Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China; Shanghai Key Laboratory of Reproduction and Development, Shanghai, China; Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China.
Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China; Shanghai Key Laboratory of Reproduction and Development, Shanghai, China; Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China.
Ageing Res Rev. 2024 Jun;97:102292. doi: 10.1016/j.arr.2024.102292. Epub 2024 Apr 4.
Age-related aneuploidy in human oocytes is a major factor contributing to decreased fertility and adverse reproductive outcomes. As females age, their oocytes are more prone to meiotic chromosome segregation errors, leading primarily to aneuploidy. Elevated aneuploidy rates have also been observed in oocytes from very young, prepubertal conceptions. A key barrier to developing effective treatments for age-related oocyte aneuploidy is our incomplete understanding of the molecular mechanisms involved. The challenge is becoming increasingly critical as more people choose to delay childbearing, a trend that has significant societal implications. In this review, we summarize current knowledge regarding the process of oocyte meiosis and folliculogenesis, highlighting the relationship between age and chromosomal aberrations in oocytes and embryos, and integrate proposed mechanisms of age-related meiotic disturbances across structural, protein, and genomic levels. Our goal is to spur new research directions and therapeutic avenues.
人类卵母细胞的年龄相关非整倍体是导致生育能力下降和不良生殖结局的主要因素。随着女性年龄的增长,其卵母细胞更容易发生减数分裂染色体分离错误,主要导致非整倍体。在非常年轻的、青春期前的受孕的卵母细胞中也观察到了升高的非整倍体率。开发针对年龄相关卵母细胞非整倍体的有效治疗方法的主要障碍是我们对所涉及的分子机制的不完全理解。随着越来越多的人选择延迟生育,这种趋势具有重大的社会意义,因此挑战变得越来越关键。在这篇综述中,我们总结了关于卵母细胞减数分裂和卵泡发生过程的现有知识,重点介绍了年龄与卵母细胞和胚胎中染色体异常之间的关系,并整合了跨结构、蛋白质和基因组水平的与年龄相关的减数分裂障碍的拟议机制。我们的目标是激发新的研究方向和治疗途径。