Schatten Heide, Sun Qing-Yuan
Department of Veterinary Pathobiology, University of Missouri, 1600 E Rollins Street, Columbia, MO 65211, USA.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China.
Reprod Fertil Dev. 2015 Jul;27(6):934-43. doi: 10.1071/RD14493.
The effects of oocyte aging on meiotic spindle dynamics have been well recognised, but the mechanisms underlying the effects are not well understood. In this paper we review the role of centrosomes and the microtubule cytoskeleton in meiotic spindle formation and maintenance, and the impact of oocyte aging on spindle integrity resulting in centrosome and microtubule dysfunctions that are associated with aneuploidy. Loss of spindle integrity includes dispersion of proteins from the centrosome core structure and loss of attachment of microtubules to centrosomes and kinetochores, which will result in abnormal chromosome separation. The inability of centrosomal proteins to accurately associate with the centrosome structure may be the result of destabilisation of the core structure itself or of microtubule destabilisation at the centrosome-facing microtubule areas that are acetylated in fresh oocytes but may not be acetylated in aging oocytes. Microtubule destabilisation prevents accurate motor-driven transport of centrosomal proteins along microtubules to form and maintain a functional centrosome. Other factors to form and maintain the MII spindle include signal transductions that affect microtubule dynamics and stability. Understanding the mechanisms underlying centrosome and microtubule dysfunctions during oocyte aging will allow diagnosis and analysis of oocyte quality and abnormalities as important aspects for targeted treatment of aging oocytes to extend or restore viability and developmental capacity. New therapeutic approaches will allow improvements in reproductive success rates in IVF clinics, as well as improvements in reproductive success rates in farm animals. This review is focused on: (1) centrosome and microtubule dynamics in fresh and aging oocytes; (2) regulation of centrosome and/or microtubule dynamics and function; and (3) possible treatments to extend the oocyte's reproductive capacity and viability span.
卵母细胞老化对减数分裂纺锤体动力学的影响已得到充分认识，但其影响背后的机制尚不清楚。在本文中，我们综述了中心体和微管细胞骨架在减数分裂纺锤体形成和维持中的作用，以及卵母细胞老化对纺锤体完整性的影响，这种影响导致与非整倍体相关的中心体和微管功能障碍。纺锤体完整性的丧失包括蛋白质从中心体核心结构的分散以及微管与中心体和动粒的附着丧失，这将导致染色体分离异常。中心体蛋白无法准确地与中心体结构结合，可能是核心结构本身不稳定的结果，也可能是在新鲜卵母细胞中乙酰化但在老化卵母细胞中可能未乙酰化的面向中心体的微管区域微管不稳定的结果。微管不稳定阻止了中心体蛋白沿微管的精确运动驱动运输，从而无法形成和维持功能性中心体。形成和维持MII纺锤体的其他因素包括影响微管动力学和稳定性的信号转导。了解卵母细胞老化过程中中心体和微管功能障碍的机制，将有助于诊断和分析卵母细胞质量及异常情况，这是针对性治疗老化卵母细胞以延长或恢复其活力和发育能力的重要方面。新的治疗方法将提高体外受精诊所的生殖成功率，以及提高农场动物的生殖成功率。本综述重点关注：（1）新鲜和老化卵母细胞中的中心体和微管动力学；（2）中心体和/或微管动力学及功能的调节；（3）延长卵母细胞生殖能力和活力的可能治疗方法。
