Howe Katie, FitzHarris Greg
Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Biol Reprod. 2013 Sep 27;89(3):71. doi: 10.1095/biolreprod.113.112151. Print 2013 Sep.
Errors in chromosome segregation in oocytes and early embryos lead to embryo aneuploidy, which contributes to early pregnancy loss. At the heart of chromosome segregation is the spindle, a dynamic biomechanical machine fashioned from microtubules, which is tasked with gathering and sorting chromosomes and dispatching them to the daughter cells at the time of cell division. Understanding the causes of segregation error in the oocyte and early embryo will undoubtedly hinge on a thorough understanding of the mechanism of spindle assembly and function in these highly specialized cellular environments. The recent advent of live imaging approaches to observe chromosome segregation in real-time in oocytes and embryos, paired with gene-silencing techniques and specific inhibition for assessing the function of a protein of interest, has led to a substantial advance in our understanding of chromosome segregation in early mammalian development. These studies have uncovered numerous mechanistic differences between oocytes, embryos, and traditional model systems. In addition, a flurry of recent studies using naturally aged mice as the model for human aging have begun to shed light on the increased levels of aneuploidy seen in embryos from older mothers. Here we review these recent developments and consider what has been learned about the causes of chromosome missegregation in early development.
卵母细胞和早期胚胎中的染色体分离错误会导致胚胎非整倍体,这是早期妊娠丢失的一个原因。染色体分离的核心是纺锤体,它是一种由微管构成的动态生物机械装置,其任务是在细胞分裂时收集和分类染色体,并将它们分配到子细胞中。要理解卵母细胞和早期胚胎中分离错误的原因,无疑取决于对这些高度特化细胞环境中纺锤体组装和功能机制的透彻理解。最近出现的实时观察卵母细胞和胚胎中染色体分离的活体成像方法,与用于评估感兴趣蛋白质功能的基因沉默技术和特异性抑制方法相结合,使我们对早期哺乳动物发育中染色体分离的理解有了实质性进展。这些研究揭示了卵母细胞、胚胎和传统模型系统之间在机制上的许多差异。此外,最近一系列以自然衰老小鼠作为人类衰老模型的研究,已开始阐明老年母亲的胚胎中非整倍体水平升高的原因。在此,我们综述这些最新进展,并思考在早期发育中关于染色体错误分离原因所了解到的情况。