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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摘要在儿童中，包括躯干肥胖、高血糖和高脂血症在内的一系列代谢功能障碍患病率增加，对少数族裔人口的影响不成比例，并增加了患上长期不良疾病的风险期限结果。虽然遗传因素是造成这种增长的部分原因，但这些疾病也有很大的环境因素。在可疑的环境因素中，产前应激源包括与不良童年经历有关的母亲抑郁、焦虑和慢性压力；潜在的机制仍然知之甚少。基因和宫内环境相互作用的一种方式引发疾病的起因是通过表观遗传修饰。事实上，像社交这样的环境暴露应激可导致促进食欲、饱腹感和营养的可察觉的长期变化。获取、新陈代谢和脂肪沉积。然而，这些基因所针对的表观基因组区域应激源仍然不清楚，主要是因为可用的基因组规模的阵列数据是用提取的DNA来测量的来自可接近的组织，如血液--但表观遗传标记因细胞类型和测量的细胞而有很大不同类型可能与代谢功能障碍无关。例外是亲本来源的胞嘧啶甲基化标记控制基因组印迹的区域，称为印迹控制区(ICR)。这些区域的甲基化是在组织规范之前很早就建立了，因此在组织中是相似的。ICRs的异常甲基化在外周血液中可检测到与许多代谢性疾病有关，使ICRs成为治疗的良好靶点代谢性疾病的调查。直到最近，只有24个ICR已知，限制了这些ICR的范围调查。我们的团队最近确定了控制DNA甲基化标记的完整谱系基因组印迹；在这里，我们试图利用这些ICR来识别与以下相关的甲基化模式儿童代谢功能障碍。我们将检验这一假设，即产前应激显著增加风险。儿童心脏代谢功能障碍，ICR可检测到的表观遗传扰动起中介作用这些联想。我们还将评估地中海等抗炎饮食的程度- 风格饮食改变了这些影响。我们将利用我们现有队列资源中的数据和生物样本新生儿表观遗传学研究和怀孕期间的压力与健康，750多名妇女和她们的从怀孕3个月开始对儿童进行跟踪，现在儿童的年龄从2岁到15岁不等。我们会验证地中海式饮食在产前通过以下途径减轻产前压力对健康影响的假设表观遗传机制。这将为表观遗传指纹与社会压力之间的联系提供急需的数据儿童的代谢结果集群，为以饮食控制为重点的临床试验铺平了道路以减轻各种产前暴露的影响。