Prenatal Exposure to Metal Mixtures: Childhood Adiposity and Adipokines

项目摘要 先前的研究已经确定了产前暴露于单一类别的内分泌激素之间的关联， 干扰化学物质（EDCs）和代谢疾病的发展。然而，很少有研究检查 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 同时暴露于多种具有相同作用机制的内分泌干扰物。拟议的研究将 使用新的统计方法检查环境混合物，以评估产前暴露对 金属的混合物，其中一些是已知的内分泌干扰物和肥胖，对儿童的代谢轨迹， 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（mtDNA Acn），作为氧化应激和炎症的生物标志物，在怀孕期间和出生时， 这可能介导儿童肥胖症的发展。这项研究将利用已经收集的数据， Viva项目，一项纵向前瞻性出生前队列研究，旨在检查出生期间发生的事件 早期发育影响生命过程中的健康结果。两千多名母亲参加了 这项研究在1999年至2002年期间在马萨诸塞州东部进行了首次产前检查，并详细介绍了 在怀孕期间，出生时和不同的时间进行访谈，问卷调查和样本收集。 发展时间点。拟议的分析将使用在妊娠期间、出生时和 7岁（童年中期）和12岁（青春期早期）。产前金属已经被测量， 在妊娠前三个月期间收集的母体红细胞（RBC）中定量。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的一个主要优势是其独特的特性 体重增加和肥胖，这是纵向测量使用敏感的肥胖措施， 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，以评估出生时的代谢功能和DXA扫描测量，以客观评估肥胖 分别是7岁和12岁。我们将使用mtDNAc n和端粒长度，在第二次产前测量， 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 有助于阐明介导内分泌干扰物与儿童之间联系的潜在分子途径 肥胖本提案中概述的研究将有助于对累积的 子宫内暴露于多种内分泌干扰物的影响，并可能确定潜在的新的干预目标， 妇女

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.