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: 2889117
• 负责人: DAVID Mark BATTAGLIA
• 金额: $ 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2889117
• 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查母亲衰老对 人类卵母细胞减数分裂的过程。试图生育的女性 当她们过了生育的黄金年龄， 卵母细胞不分离的发生率增加。这表示 这是一个重大的公共卫生问题，因为越来越多的妇女正试图 在比以往任何时候都更老的年龄繁殖。的原因 不分离是由于减数分裂过程中的异常， 还有待确认我们有年轻人（20-25岁）和老年人的数据 女性（40-45岁），证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。 这表明减数分裂的调控机制 纺锤体组装在老年妇女中改变，从而导致不规则的 纺锤体和异常染色体位置。在我们的国家中， 了解人类卵母细胞减数分裂的不同阶段 特别是关于衰老的影响。我们的具体目标是 三方面：1）检查染色体运动的模式， 来自不同年龄组的活人类卵母细胞减数分裂， 调节蛋白的表达和位置的检查 参与减数分裂纺锤体组装。2)分析招聘 被认为参与减数分裂的特异性胞质结构域， 人类卵母细胞3)使用老化的动物模型来检查类似的方面 减数分裂的过程。我们假设母亲的衰老 引起染色体运动和改变的时间和空间变化 在减数分裂的早期阶段的特定调控元件。这些 实验将提供信息的机制负责 由于高龄产妇经常发生的不分离。 鉴定卵母细胞中的特定分子事件， 受年龄影响的人将导致预防 老年妇女的不分离。

项目成果

Ovarian follicular concentrations of activin, follistatin, inhibin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3, and vascular endothelial growth factor in spontaneous menstrual cycles of normal women of advanced

自发月经时卵巢卵泡中激活素、卵泡抑素、抑制素、胰岛素样生长因子 I (IGF-I)、IGF-II、IGF 结合蛋白-2 (IGFBP-2)、IGFBP-3 和血管内皮生长因子的浓度

• DOI: 10.1210/jcem.85.12.7056
• 发表时间: 2000
• 期刊: The Journal of clinical endocrinology and metabolism
• 作者: Klein,NA;Battaglia,DE;Woodruff,TK;Padmanabhan,V;Giudice,LC;Bremner,WJ;Soules,MR
• 通讯作者: Soules,MR

Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women.

• DOI: 10.1093/oxfordjournals.humrep.a019080
• 发表时间: 1996-10
• 期刊: Human reproduction
• 影响因子: 6.1
• 作者: David E. Battaglia;P. Goodwin;Nancy A. Klein;M. Soules