Prenatal Exposure to Metal Mixtures: Childhood Adiposity and Adipokines

产前接触金属混合物：儿童肥胖和脂肪因子

基本信息

批准号：
10387995
负责人：
Anna Rose Smith
金额：
$ 2.89万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
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：
2022-02-01 至 2022-08-12
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10387995
关键词：
Address Adipocytes Adolescent Adult Children Adverse effects Affect Age Animals Antioxidants Arsenic Barium Biological Markers Birth Body mass index Cadmium Cesium Chemicals Child Childhood Chronic Disease DNA copy number Data Development Disease Disease Outcome Disease susceptibility Dual-Energy X-Ray Absorptiometry Endocrine Endocrine Disruptors Energy Intake Enrollment Environmental Exposure Environmental Health Environmental Risk Factor Erythrocytes Event Exposure to First Pregnancy Trimester Functional disorder Health Health Policy Hormones Human Individual Infant Inflammation Intervention Interview Knowledge Lead Length Leptin Life Cycle Stages Magnesium Manganese Massachusetts Maternal Exposure Measurement Measures Mediating Mediation Mediator of activation protein Mercury Metabolic Metabolic Diseases Metabolic Marker Metabolic dysfunction Metabolic syndrome Metabolism Metal exposure Metals Mitochondrial DNA Modeling Molecular Molecular Epidemiology Mothers Obesity Obesity Epidemic Outcome Oxidative Stress Pathway interactions Patients Perinatal Physical activity Population Pregnancy Pregnant Women Prenatal care Public Health Public Health Practice Questionnaires Research Research Project Grants Risk Scanning Scientist Second Pregnancy Trimester Selenium Statistical Methods Statistical Models Telomere Shortening Testing Time Training Umbilical Cord Blood Weight Gain Zinc adipokines adiponectin cohort cost design early adolescence environmental chemical exposed human population in utero insight mitochondrial dysfunction molecular marker novel obesity in children obesogen overweight child postnatal prenatal prenatal exposure prospective sample collection telomere

项目摘要

PROJECT SUMMARY Prior studies have identified associations between prenatal exposure to single classes of endocrine disrupting chemicals (EDCs) and the development of metabolic disease. However, few studies have examined the effect of mixtures of chemicals on perinatal and pediatric outcomes, despite evidence that pregnant women are exposed to multiple EDCs simultaneously that share mechanisms of action. The proposed research will examine environmental mixtures using novel statistical methods to evaluate the effect of prenatal exposure to mixtures of metals, some of which are known EDCs and obesogens, on metabolic trajectory of children during development. It will also evaluate the effect of these metal mixtures on telomere length and mitochondria DNA copy number (mtDNAcn), as biomarkers of oxidative stress and inflammation, during pregnancy and at birth, which may mediate the development of childhood adiposity. This study will harness already collected data from Project Viva, a longitudinal prospective pre-birth cohort designed to examine the extent to which events during early development affect health outcomes during the life course. Over two thousand mothers were enrolled in the study at their initial prenatal visits in eastern Massachusetts between 1999 and 2002, and detailed interviews, questionnaires, and sample collection was performed during pregnancy, at birth, and at distinct developmental time points. The proposed analysis will use data collected during pregnancy, at birth, and at ages seven (mid-childhood) and twelve (early adolescence). Prenatal metals have already been measured and quantified in maternal red blood cells (RBCs) collected during the first trimester of pregnancy. These include six nonessential metals (arsenic, barium, cadmium, cesium, mercury, lead) and four essential metals (magnesium, manganese, selenium, and zinc). A major strength of Project Viva is the unique characterization of weight gain and adiposity, which was measured longitudinally using sensitive measures of adiposity and metabolic function. We will use levels of adipocyte-secreted hormones in cord blood, including leptin and adiponectin, to assess metabolic function at birth and DXA scan measurements to objectively assess adiposity at ages seven and twelve. We will use mtDNAcn and telomere length, measured prenatally during the second trimester of pregnancy and at birth, as biomarkers of oxidative stress and inflammation. These biomarkers will help elucidate the potential molecular pathway mediating the association between EDCs and childhood obesity. The research outlined in this proposal will contribute to the limited knowledge regarding the cumulative effects of in utero exposure to multiple EDCs and may identify potential new targets for intervention in pregnant women.

项目概要先前的研究已经确定了产前接触单一类别内分泌激素之间的关联破坏化学物质（EDC）和代谢疾病的发展。然而，很少有研究考察化学品混合物对围产期和儿科结局的影响，尽管有证据表明孕妇同时接触多种具有相同作用机制的 EDC。拟议的研究将使用新的统计方法检查环境混合物，以评估产前暴露的影响金属混合物（其中一些是已知的 EDC 和致肥胖物质）对儿童代谢轨迹的影响发展。它还将评估这些金属混合物对端粒长度和线粒体 DNA 的影响拷贝数（mtDNAcn），作为怀孕期间和出生时氧化应激和炎症的生物标志物，这可能会介导儿童肥胖的发展。这项研究将利用已经收集的数据 Project Viva 是一个纵向前瞻性的产前队列，旨在检查出生期间事件的程度早期发育影响生命历程中的健康结果。超过两千名妈妈报名参加该研究于 1999 年至 2002 年间在马萨诸塞州东部进行了首次产前检查，并详细介绍了访谈、问卷调查和样本收集是在怀孕期间、出生时和不同的时间进行的。发育时间点。拟议的分析将使用怀孕期间、出生时和出生时收集的数据。七岁（童年中期）和十二岁（青春期早期）。产前金属已被测量并对妊娠前三个月收集的母体红细胞 (RBC) 进行定量。这些包括六种非必需金属（砷、钡、镉、铯、汞、铅）和四种必需金属（镁、锰、硒和锌）。 Project Viva 的主要优势是独特的特征体重增加和肥胖，这是使用肥胖和肥胖的敏感测量方法纵向测量的代谢功能。我们将使用脐带血中脂肪细胞分泌的激素水平，包括瘦素和脂联素，用于评估出生时的代谢功能和 DXA 扫描测量，以客观评估肥胖七岁和十二岁。我们将使用在第二次产前测量的 mtDNAcn 和端粒长度妊娠三个月和出生时，作为氧化应激和炎症的生物标志物。这些生物标志物将帮助阐明介导 EDC 与童年之间关联的潜在分子途径肥胖。本提案中概述的研究将有助于补充有关累积的有限知识子宫内暴露于多种 EDC 的影响，并可能确定妊娠干预的潜在新目标女性。