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的过程，这是人类概念中最常见的染色体异常，也是造成妊娠丧失和严重智力低下的主要原因。提高产妇年龄是唯一既定的危险因素。该项目（a）测试该关联是否反映了卵巢中的加速衰老，并且（b）检查了与与早熟卵巢衰老相关的遗传特征的联系。我们假设三体菌是卵母细胞库（卵巢年龄）的大小而产生的，而在任何给定的年代年龄时，池较小的女性中三体疾病风险增加。卵母细胞的数量在出生前最高，随着女性年龄的增长。在任何给定的年代年龄，这个数字因女人而异。小水池可能是由于胎儿发育过程中卵母细胞产生的减少或加速卵母细胞（损失）所致。关于这两个过程的原因知之甚少。较小的卵母细胞池的一个可能原因是FMR1基因上的CGG重复大小，这与早产卵巢衰竭有关。我们假设FMR1重复大小与三体性有关。该应用程序利用已经收集的数据。对于卵母细胞池假设的测试，主要数据衍生出100名三叶孕妇丧失（病例）和279个活产的对照，以及两个妊娠损失的子公司比较组。卵母细胞池大小的激素指标包括抗Mullerian激素，卵泡刺激激素和抑制素B。对于与FMR1重复大小的关联测试，该样品包括206个三体菌病例和548个对照组，以及两个子公司比较组。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同一年龄的实时节育措施中的卵巢年龄更高，并评估关联的特异性。 2。测试母体FMR1重复大小在三体病例中是否比对照组长。 3。通过检查FMR1重复大小与激素指标的关系来阐明机制。确认假设对三体形成机制的研究以及咨询妇女有关怀孕的潜在应用具有影响。该应用程序旨在阐明导致三体性的过程，这是人类概念中最常见的染色体异常，也是妊娠丧失和严重智力低下的主要原因。它检验了以下假设：与产妇年龄的牢固关联反映了卵巢的加速衰老。该项目对希望将育儿推迟到年龄较大的妇女咨询咨询具有重要的临床意义。