Prenatal stress and diet, and the fetal epigenome

产前压力和饮食，以及胎儿表观基因组

基本信息

批准号：
10665054
负责人：
Cathrine Hoyo
金额：
$ 63.79万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10665054
关键词：
Adherence Adolescent Adult Affect African American Age Alanine Transaminase Alleles Animals Anti-Inflammatory Agents Antioxidants Anxiety Bioinformatics Biological Black race Blood Body mass index Cardiovascular Diseases Cardiovascular system Cells Central obesity Child Childhood Cholesterol Chronic Chronic stress Clinical Clinical Trials County Cues Cytosine DNA DNA Methylation Data Deposition Desire for food Diet Disease Disparity Early identification Enrollment Environment Environmental Exposure Epigenetic Process Ethnic Origin Exposure to Fasting Fatty acid glycerol esters Financial Hardship Fingerprint Free Radicals Functional disorder Future Gene Expression Genes Genetic Genetic Variation Genome Genomic Imprinting Germ Layers Gestational Diabetes H19 gene Health Hispanic Hispanic Populations Human Hyperglycemia Hyperlipidemia Hypertension IGF2 gene Individual Intervention Investigation Knowledge Life Life Cycle Stages Link Liver Dysfunction Measures Mediating Mediator Mediterranean Diet Mental Depression Metabolic Metabolic Diseases Metabolic dysfunction Metabolism Methylation Minority Groups Modification Moods Mothers Newborn Infant Non-Insulin-Dependent Diabetes Mellitus North Carolina Nutrient Obesity Outcome Oxidative Stress Parents Participant Pathway interactions Peripheral Policies Pregnancy Pregnant Women Prevalence Prevention Process Production Proxy Public Health Publishing Records Reporting Resources Risk Risk Factors Role Sampling Satiation Specific qualifier value Specimen Stress Testing Tissues Triglycerides Woman adverse childhood events adverse pregnancy outcome aged cardiometabolic risk cell type cohort density depressive symptoms dietary adherence dietary manipulation epigenome ethnic minority excessive weight gain fetal genome-wide imprint in utero insight maternal anxiety maternal depression maternal risk maternal stress methylation pattern mother nutrition novel obesity in children offspring perceived discrimination peripheral blood prenatal prenatal exposure prenatal stress racial minority response social adversity social stress social stressor stressor systemic inflammatory response waist circumference

项目摘要

Maternal stress and diet, and the fetal epigenome Abstract In children, a cluster of metabolic dysfunction including truncal obesity, hyperglycemia, and hyperlipidemia are increasing in prevalence, disproportionately affect minority populations, and increase the risk for adverse long- term outcomes. While genetic factors underlie some of this increase, these conditions also have a large environmental component. Among suspected environmental contributors are prenatal stressors including maternal depression and anxiety and chronic stress associated with adverse childhood experiences; the underlying mechanisms remain poorly understood. One way in which genes and the in utero environment can interact to trigger the initiation of disease is through epigenetic modifications. In fact, environmental exposures like social stress can cause detectable long-term changes in pathways that contribute to appetite and satiety, nutrient acquisition, metabolism, and fat deposition. However, the regions of the epigenome that are targeted by these stressors remains unclear, primarily because available genome-scale array data are measured in DNA derived from accessible tissues, such as blood—but epigenetic marks vary widely by cell type, and the measured cell types may not be relevant to metabolic dysfunction. The exception is parent-of origin cytosine methylation marks that control genomic imprinting, known as imprint control regions (ICRs). Methylation of these regions is established early, before tissue specification, and therefore is similar across tissues. Aberrant methylation of ICRs detectable in peripheral blood is implicated in numerous metabolic diseases, making ICRs promising targets for investigations of metabolic diseases. Until recently, only 24 ICRs were known, limiting the scope of these investigations. Our group recently identified the complete repertoire of DNA methylation marks that control genomic imprinting; here, we seek to leverage these ICRs to identify methylation patterns associated with metabolic dysfunction in children. We will test the hypothesis that prenatal stress substantially increases the risk of cardiometabolic dysfunction among children, and that detectable epigenetic perturbations at ICRs mediate these associations. We also will evaluate the extent to which anti-inflammatory diets such as the Mediterranean- style diet modify these effects. We will leverage data and biological samples from our existing cohort resources of the Newborn Epigenetics Study and Stress and Health In Pregnancy, where more than 750 women and their children have been followed from 3 months gestation, and children now range in age from 2 to 15 years. We will test the hypothesis that a Mediterranean-style diet prenatally, mitigates health effects of prenatal stress via epigenetic mechanisms. This will provide much-needed data on the epigenetic fingerprint linking social stressors to the cluster of metabolic outcomes in children, paving the way for clinical trials focused on dietary manipulation to mitigate the effects of a wide variety of prenatal exposures.

母体压力和饮食以及胎儿表观基因组抽象的在儿童中，包括截短肥胖，高血糖和高脂血症在内的一组代谢功能障碍是患病率的增加，不成比例地影响少数群体，并增加广告的风险很长术语成果。尽管遗传因素是其中一些增加的基础，但这些条件也很大环境组成部分。在可疑的环境贡献者中，有产前压力源包括孕产妇抑郁，焦虑以及与童年不良经历相关的慢性压力；基础机制仍然很少理解。基因和子宫内环境中的一种方法可以与触发疾病的主动性是通过表观遗传修饰。实际上，环境暴露等社会压力会导致可检测到的长期变化，导致食欲和饱腹感，营养素获取，代谢和脂肪沉积。但是，这些目标是由这些区域的压力源不清楚，主要是因为可用的基因组规模阵列数据是在衍生的DNA中测量的从可访问的时机（例如血液）中，但表观遗传标记因细胞类型而差异很大，并且测得的细胞类型可能与代谢功能障碍无关。例外是父母的胞质甲基化标记该控制基因组印记，称为烙印控制区（ICR）。这些区域的甲基化是在组织规范之前建立，因此在整个组织之间相似。 ICR的异常甲基化在多种代谢疾病中暗示在外周血中检测到对代谢疾病的调查。直到最近，只有24个ICR才知道，限制了这些范围调查。我们的小组最近确定了控制的DNA甲基化标记的完整曲目基因组印迹；在这里，我们试图利用这些ICR来识别与儿童代谢功能障碍。我们将检验以下假设，即产前压力大大增加了风险儿童的心脏代谢功能障碍，以及在ICRS中可检测到的表观遗传扰动这些关联。我们还将评估抗炎饮食（例如地中海）的程度样式饮食会改变这些影响。我们将利用现有队列资源的数据和生物样本在怀孕的新生儿表观遗传学研究与压力与健康中，有750多名妇女及其从妊娠3个月开始，儿童就受到了追踪，现在儿童的年龄从2至15岁不等。我们将检验地中海风格饮食产前饮食的假设可以减轻产前压力的健康作用表观遗传机制。这将提供有关与社会压力联系的表观遗传指纹的急需数据到儿童代谢结果的簇，为临床试验铺平了道路减轻各种产前暴露的影响。