Measuring the effects of prenatal alcohol exposure on placenta methylation

测量产前酒精暴露对胎盘甲基化的影响

• 批准号: 8739309
• 负责人: Kyriacos Markianos
• 金额: $ 8.55万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-24 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8739309
• 关键词: Aberrant DNA Methylation; Alcohol consumption; Alcohols; Biological Markers; Cell division; Child health care; Communities; Congenital Abnormality; DNA; DNA Methylation; Data Set; Development; Diabetes Mellitus; Disease; Enrollment; Environmental Exposure; Epigenetic Process; Ethanol toxicity; Evaluation; Exposure to; Family; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Development; Fetus; First Pregnancy Trimester; Foundations; Future; Genetic; Goals; Health; Heavy Drinking; Histopathology; Human; Individual; Infant; Injury; Interview; Lead; Left; Life; Malnutrition; Measurement; Measures; Methylation; Morbidity - disease rate; National Institute of Child Health and Human Development; Outcome; Pathologist; Pattern; Perinatal Exposure; Phenotype; Placenta; Population; Pregnancy; Pregnant Women; Prevention; Process; Prospective Studies; Reporting; Research Personnel; Risk; Role; Sampling; Site; Smoking; Societies; Specimen; Sudden infant death syndrome; Technology; Time; Tissues; Woman; Work; adverse outcome; alcohol abstinence; alcohol consumption during pregnancy; alcohol exposure; base; cigarette smoking; cohort; cost; experience; fetal; follow-up; gene environment interaction; genome wide methylation; high risk; mortality; novel strategies; nutrition; postnatal; prenatal; prospective; public health relevance; stillbirth

DESCRIPTION (provided by applicant): Environmental challenges such as maternal alcohol exposure, smoking, or malnutrition, likely leave their mark on the developing fetus via epigenetic changes, particularly changes in DNA methylation. Epigenetic changes can be a marker of past environmental challenges, but can also lead to disease. The placenta, an easily available tissue for study, is ideal for identifying significant epigenetic changes associated with early fetal alcool exposure. Here we utilize a unique data set, placentas collected by the Safe Passage Study (PASS), to conduct the first study to measure the potential effect of alcohol exposure in placenta methylation. We will measure genome wide methylation using the Illumina 450k methylation array technology in a paired sample of 20 placentas from women who reported heavy drinking during early pregnancy compared to those from 20 women who abstained from alcohol throughout pregnancy. The Safe Passage Study is the first prospective, longitudinal, large-scale, and hypothesis-driven study of the relationship between prenatal alcohol toxicity and mortality and morbidity in the human fetus and infant. Upon completion 12,000 pregnant women will be enrolled in PASS and placenta samples will be collected for a random subset (~2700) from high-risk populations for prenatal alcohol exposure, SIDS, stillbirth, and FASD in a prospective study with follow-up of their infants to one postnatal year. Thus this is an ideal setting for this and future studies of placenta methylation changes due to alcohol exposure and their effects on fetal health.

描述（由申请人提供）：环境挑战，如母亲酒精暴露，吸烟或营养不良，可能会通过表观遗传变化，特别是DNA甲基化的变化，在发育中的胎儿上留下印记。表观遗传变化可能是过去环境挑战的标志，但也可能导致疾病。胎盘是一种容易获得的研究组织，是鉴定与早期胎儿酒精暴露相关的显着表观遗传变化的理想材料。在这里，我们利用一个独特的数据集，胎盘收集的安全通道研究（PASS），进行第一项研究，以衡量酒精暴露在胎盘甲基化的潜在影响。我们将使用Illumina 450k甲基化阵列技术测量20个胎盘的配对样本中的全基因组甲基化，这些胎盘来自报告在怀孕早期大量饮酒的女性，与来自20名在整个怀孕期间戒酒的女性的胎盘进行比较。安全通道研究是第一个前瞻性，纵向，大规模和假设驱动的研究产前酒精中毒和人类胎儿和婴儿的死亡率和发病率之间的关系。完成后，PASS将招募12，000名孕妇，并在一项前瞻性研究中从产前酒精暴露、SIDS、死产和FASD的高风险人群中随机收集胎盘样本（约2700例），并对其婴儿进行随访至出生后一年。因此，这是一个理想的设置为这个和未来的研究胎盘甲基化的变化，由于酒精暴露及其对胎儿健康的影响。