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.

母亲压力和饮食以及胎儿表观基因组抽象的在儿童中，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不断上升，对少数群体产生了不成比例的影响，并增加了长期不良反应的风险虽然遗传因素是造成这种增加的部分原因，但这些条件也有很大影响。环境因素是可疑的环境因素之一，其中包括产前压力因素。与不良童年经历相关的母亲抑郁、焦虑和慢性压力；基因和子宫内环境相互作用的一种机制仍然知之甚少。事实上，诸如社交等环境暴露是通过表观遗传修饰引发疾病的。压力会导致促进食欲和饱腹感、营养物质的途径发生可检测到的长期变化然而，这些目标的表观基因组区域。压力源仍不清楚，主要是因为可用的基因组规模阵列数据是在 DNA 衍生的中测量的来自可接近的组织，例如血液，但表观遗传标记因细胞类型而异，并且测量的细胞类型可能与代谢功能障碍无关，但亲本胞嘧啶甲基化标记除外。控制基因组印记，称为这些区域的印记控制区（ICR）。在组织特化之前就已建立，因此跨组织的 ICR 异常甲基化是相似的。外周血中可检测到的 ICR 与许多代谢疾病有关，这使得 ICR 有希望成为治疗疾病的靶标。直到最近，已知的 ICR 仅有 24 种，这限制了这些研究的范围。我们的小组最近确定了控制 DNA 甲基化标记的完整库。基因组印记；在这里，我们寻求利用这些 ICR 来识别与我们将检验产前压力显着增加风险的假设。儿童心脏代谢功能障碍的研究，以及 ICR 介导的可检测的表观遗传扰动我们还将评估地中海饮食等抗炎饮食的程度。我们将利用现有队列资源中的数据和生物样本来改变这些影响。新生儿表观遗传学研究和妊娠期压力与健康研究，超过 750 名妇女及其她们的我们将从怀孕 3 个月开始对儿童进行随访，目前儿童的年龄范围为 2 岁至 15 岁。检验以下假设：产前地中海式饮食可通过以下方式减轻产前压力对健康的影响：表观遗传机制。这将为连接社会压力源的表观遗传指纹提供急需的数据。儿童代谢结果的集群，为专注于饮食控制的临床试验铺平道路减轻各种产前暴露的影响。