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

• 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
• 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

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.

项目摘要 先前的研究已经确定了产前暴露于单一类内分泌之间的关联 破坏化学物质（EDC）和代谢疾病的发展。但是，很少有研究检查 尽管孕妇证据表明，化学物质混合物对围产期和小儿结局的影响 共享行动机制的同时接触多个EDC。拟议的研究将 使用新型统计方法检查环境混合物，以评估产前暴露的影响 金属的混合物（其中一些是已知的EDC和肥胖症）在儿童的代谢轨迹上 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），作为氧化应激和炎症的生物标志物，在怀孕和出生时， 这可能会介导童年肥胖的发展。这项研究将利用已经从 Viva项目，纵向前瞻性出生前队列，旨在检查在多大程度上 早期发展会影响人生过程中的健康状况。超过两千个母亲被招募 这项研究在1999年至2002年之间在马萨诸塞州东部的最初产前访问中进行的研究，并详细 访谈，问卷调查和样本收集是在怀孕，出生时和不同的 发展时间点。拟议的分析将使用怀孕，出生时和在 七岁（年龄段）和十二岁（青春期早期）。产前金属已经测量，并且 在怀孕的头三个月收集的母体红细胞（RBC）中进行了量化。这些包括 六种非必需金属（砷，钡，镉，瓶，汞，铅）和四种必需金属 （镁，锰，硒和锌）。 Viva项目的主要优势是独特的特征 体重增加和肥胖，它是使用敏感的肥胖度量和 代谢功能。我们将使用脐带血中的脂肪细胞分泌激素的水平，包括瘦素和 脂联素，评估出生时代谢功能和DXA扫描测量值以客观评估肥胖 七岁和十二岁。我们将使用mtdnacn和端粒长度，在第二个 怀孕和出生时，作为氧化应激和炎症的生物标志物。这些生物标志物会 帮助阐明介导EDC与童年之间关联的潜在分子途径 肥胖。该提案中概述的研究将有助于有关累积的有限知识 子宫内暴露于多个EDC的影响，并可能确定潜在的新目标来干预怀孕 女性。