Trisomy and ovarian age: An epidemiologic study

三体性和卵巢年龄：流行病学研究

• 批准号: 7587307
• 负责人: Jennie Katherine Kline
• 金额: $ 36.39万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7587307
• 关键词: Age; Aging; Antral; Area; Birth; CGG repeat; Characteristics; Chromosome abnormality; Clinical; Competence; Conceptions; Counseling; Couples; DNA; Data; Delayed Childbearing; Epidemiologic Studies; Expenditure; FMR1; FMR1 Gene; FMR1 repeat; Fetal Development; Follicle Stimulating Hormone; Fragile X Syndrome; Genetic; Goals; High Risk Woman; Hormonal; Hormones; Human; Interview; Length; Link; Maternal Age; Measures; Meiosis; Menstrual cycle; Mental Retardation; Oocytes; Ovarian; Ovary; Patau' s syndrome; Physiological Processes; Pregnancy; Pregnancy loss; Premature Ovarian Failure; Process; Production; Research; Risk; Risk Factors; Sample Size; Sampling; Serum; Specificity; Spontaneous abortion; Testing; Time; Trisomy; Trisomy X syndrome; Woman; X Inactivation; advanced maternal age; age related; child bearing; cohort; comparison group; inhibin B; premature

DESCRIPTION (provided by applicant): The long-term goal is to elucidate the processes leading to trisomy, the most frequent chromosomal anomaly among human conceptions and a major cause of pregnancy loss and severe mental retardation. Advancing maternal age is the only established risk factor. This project (a) tests whether the association reflects accelerated aging in the ovary and (b) examines connections with a genetic characteristic associated with premature ovarian aging. We hypothesize that trisomy arises as a function of the size of the oocyte pool (ovarian age), with trisomy risk increased among women with smaller pools at any given chronologic age. The number of oocytes is highest before birth and decreases as women age. At any given chronologic age, the number varies from woman to woman. Small pools may result from diminished production of oocytes during fetal development or accelerated oocyte atresia (loss). Little is known about the causes of either process. One possible cause of a smaller oocyte pool is the size of the CGG repeat on the FMR1 gene, which has been associated with premature ovarian failure. We hypothesize that FMR1 repeat size is associated with trisomy. This application draws on already collected data. For tests of the oocyte pool hypothesis, the primary data derive from 100 women with trisomic pregnancy losses (cases) and 279 controls with live births, as well as two subsidiary comparison groups with pregnancy losses. Hormonal indicators of the size of the oocyte pool include anti- Mullerian hormone, follicle stimulating hormone and inhibin B. For tests of associations with FMR1 repeat size, the sample comprises 206 trisomy cases and 548 controls, as well as two subsidiary comparison groups. The specific aims are: 1. To test whether hormone levels indicate more advanced ovarian age among trisomy cases than among live birth controls of the same chronologic age and to assess the specificity of associations. 2. To test whether maternal FMR1 repeat size is longer in trisomy cases than in controls. 3. To elucidate mechanisms by examining the relation of FMR1 repeat size to hormonal indicators. Confirmation of the hypotheses has implications both for research on mechanisms of trisomy formation and potential application for counseling women about pregnancy. This application seeks to elucidate the processes leading to trisomy, the most frequent chromosomal anomaly among human conceptions and a major cause of pregnancy loss and severe mental retardation. It tests the hypothesis that the strong association with maternal age reflects accelerated aging in the ovary. This project has important clinical implications for counseling women who wish to delay childbearing to older ages.

描述（由申请人提供）：长期目标是阐明导致三体性的过程，三体性是人类受孕中最常见的染色体异常，也是流产和严重智力低下的主要原因。孕产妇高龄是唯一确定的危险因素。该项目（a）测试这种关联是否反映了卵巢加速衰老，（b）检查与卵巢早衰相关的遗传特征的联系。我们假设三体性是卵母细胞池大小（卵巢年龄）的函数，在任何给定的实际年龄下，卵母细胞池较小的女性的三体性风险会增加。卵母细胞的数量在出生前最高，并随着女性年龄的增长而减少。在任何给定的实际年龄，这个数字因女性而异。小池可能是由于胎儿发育过程中卵母细胞产量减少或卵母细胞闭锁（丢失）加速造成的。对于这两个过程的原因知之甚少。卵母细胞池较小的一个可能原因是 FMR1 基因上 CGG 重复的大小，这与卵巢早衰有关。我们假设 FMR1 重复大小与三体性相关。该应用程序利用了已经收集的数据。为了检验卵母细胞池假说，主要数据来自 100 名三体妊娠流产女性（病例）和 279 名活产对照者，以及两个妊娠流产的附属对照组。卵母细胞库大小的激素指标包括抗苗勒氏管激素、卵泡刺激素和抑制素 B。为了测试与 FMR1 重复大小的关联，样本包括 206 个三体病例和 548 个对照，以及两个辅助比较组。具体目的是： 1. 测试激素水平是否表明三体病例中的卵巢年龄比相同年龄的活产对照中的卵巢年龄更晚，并评估关联的特异性。 2. 测试三体病例中母体 FMR1 重复序列大小是否比对照更长。 3. 通过检查FMR1重复大小与激素指标的关系来阐明机制。这些假设的证实对于三体形成机制的研究和对妇女怀孕咨询的潜在应用都有影响。该申请旨在阐明导致三体性的过程，三体性是人类受孕中最常见的染色体异常，也是流产和严重智力低下的主要原因。它检验了一个假设，即与母亲年龄的密切相关反映了卵巢加速衰老。该项目对于为希望推迟生育的女性提供咨询具有重要的临床意义。