MATERNAL AGING AND MEIOTIC REPRODUCTION IN OOCYTES

母体衰老和卵母细胞减数分裂繁殖

• 批准号: 2389521
• 负责人: DAVID Mark BATTAGLIA
• 金额: $ 18.19万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2389521
• 关键词: age at pregnancy; age difference; aging; cell cycle; centrosome; chromosome movement; clinical research; egg /ovum; female; fluorescence microscopy; fluorescent dye /probe; human subject; immunocytochemistry; laboratory mouse; meiosis; microtubules; mitotic spindle apparatus; morphology; nondisjunction; paclitaxel; species difference

The goal of this research is to examine the effects of maternal aging on the process of meiosis in the human oocyte. Women attempting to reproduce when they are beyond their prime reproductive years often experience an increased incidence of nondisjunction in their oocytes. This represents a significant public health issue since more women are attempting to reproduce at an older age than ever before. The cause of the nondisjunction is due to abnormalities in the process of meiosis that have yet to be identified. We have data from younger (age 20-25) and older women (age 40-45) demonstrating that the meiotic spindle in older women is abnormal with regard to the microtubule matrix and chromosome alignment. This suggests that the regulatory mechanism responsible for meiotic spindle assembly are altered in older women, thus leading to irregular spindles and abnormal chromosome placement. There are large gaps in our knowledge of the different phases of meiosis in the human oocyte particularly with regard to the affects of aging. Our specific goals are threefold: 1) To examine the patterns of chromosome movement during meiosis in living human oocytes from different age groups followed by examination of the expression and placement of regulatory proteins involved in meiotic spindle assembly. 2) Analyze the recruitment of specific cytoplasmic domains that are thought to be involved in meiosis in the human oocyte. 3) Use an aging animal model to examine similar aspects of meiosis during maternal aging. We hypothesize that maternal aging causes temporal and spatial changes in chromosome movement and alteration of specific regulatory elements during the early phases of meiosis. These experiments will provide information on the mechanisms responsible for the nondisjunction that often occurs due to advanced maternal age. Identification of specific molecular events in the oocyte that are affected by age will lead to strategies for the prevention of nondisjunction in older women.

这项研究的目的是检验母亲老龄化对 人类卵母细胞减数分裂的过程。试图生育的女性 当他们过了最好的生殖年龄段时，通常会经历 他们的卵母细胞不分离的发生率增加。这表示一个 重大的公共卫生问题，因为越来越多的女性试图 繁殖的年龄比以往任何时候都要大。造成这一现象的原因 不分离是由于减数分裂过程中的异常 还没有确定身份。我们有年轻人(20-25岁)和年龄较大的人的数据 女性(40-45岁)表明老年女性的减数分裂纺锤体是 微管基质和染色体排列异常。 这表明负责减数分裂的调控机制 年长女性的纺锤体组装发生改变，从而导致不规则 纺锤体和异常染色体位置。我们有很大的差距 人类卵母细胞减数分裂不同阶段的认识 特别是在老龄化的影响方面。我们的具体目标是 三个方面：1)研究染色体运动的模式 不同年龄组活体人卵母细胞的减数分裂 调控蛋白的表达和定位的检测 参与减数分裂纺锤体的组装。2)分析员工招聘情况 被认为参与植物减数分裂的特定细胞质结构域 人类的卵母细胞。3)使用衰老的动物模型来检查类似的方面 在母体衰老过程中的减数分裂。我们假设母体的衰老 导致染色体运动和改变的时间和空间变化 在减数分裂早期阶段的特定调控元件。这些 实验将提供关于负责的机制的信息 由于产妇年龄较大而经常发生的不分离。 识别卵母细胞中的特定分子事件 受年龄的影响将导致制定预防策略 老年女性的不分离。