Human Maternal/Fetal Exposures to PBDEs and their Metabolites During Development

人类母体/胎儿在发育过程中接触多溴联苯醚及其代谢物

• 批准号: 8712486
• 负责人: Tracey J. Woodruff
• 金额: $ 11.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-02 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8712486
• 关键词: Adult; Affect; Affinity; Androstanes; Animals; Aryl Hydrocarbon Receptor; Binding; Biologic Characteristic; Biological; Biological Assay; Birth; Blood; California; Cell Proliferation; Characteristics; Chemical Exposure; Chemical-Induced Change; Chemicals; Cytochrome P450; Cytochromes; Data; Demographic Accounting; Development; Drug Formulations; Dust; Endocrine; Endocrine disruption; Environment; Enzymes; Epidemiologic Studies; Estrogens; Exposure to; Fetal Development; Fetal Liver; Fetal Tissues; Fetus; Flame Retardants; Food; Gene Expression; General Hospitals; Gestational Age; Growth; Hepatocyte; Hormones; Human; Immunoblotting; In Vitro; Individual; Isoenzymes; Lead; Liver; Maternal Exposure; Measurable; Measurement; Measures; Mediating; Messenger RNA; Metabolic; Metabolic Pathway; Metabolism; Nuclear Receptors; Observational Study; Organ; Organic Chemicals; Parents; Pentas; Perinatal Exposure; Phase; Placenta; Population; Pregnancy; Pregnancy Trimesters; Pregnanes; Pregnant Women; Property; Proteins; Proxy; Public Health; RNA; Rattus; Research; Resources; Risk; Role; Sampling; San Francisco; Second Pregnancy Trimester; Serum; Specimen; Termination of pregnancy; Testing; Testosterone; Thyroid Gland; Thyroid Hormones; Tissues; Toxic effect; Toxicology; Umbilical Cord Blood; United States; Woman; Xenobiotics; base; consumer product; environmental chemical; enzyme activity; estrogen-related receptor; exposed human population; fetal; human data; human fetus tissue; improved; in utero; in vivo; mRNA Expression; maternal cigarette smoking; maternal serum; neurodevelopment; novel; phenyl ether; predictive modeling; prenatal; prenatal exposure; public health relevance; reproductive; research study; steroid hormone

DESCRIPTION (provided by applicant): Our proposal tests the hypotheses that polybrominated diphenyl ethers (PBDEs) and their metabolites (OH- PBDEs) accumulate differently in the human fetal liver and placenta than in maternal serum, and that fetal exposure to PBDEs affects fetal metabolic capacity. Virtually all pregnant women in the United States are exposed to at least one and often multiple PBDEs, a class of persistent organic chemicals widely used as flame retardants in consumer products since the 1970s. PBDEs are an important public health concern, as in vitro and in vivo studies show that in utero exposure can adversely impact fetal development. Human exposure and epidemiologic studies have largely characterized in utero exposure by measuring chemicals in proxy biological specimens, such as maternal blood and umbilical cord blood collected at delivery. These samples are not necessarily representative of fetal exposures earlier in pregnancy, particularly to target organs of concern such as the liver and placenta. We propose to measure levels of PBDEs and OH-PBDEs in human maternal and fetal biological specimens from women undergoing voluntary, second trimester pregnancy terminations. Because data on chemical-induced changes in human fetal metabolic capacity are critical to understanding mechanisms of in utero toxicity but are currently lacking, we will also generate original human data on whether fetal exposures to PBDEs alter gene expression of cytochrome P450 (CYP) enzymes in the second-trimester human fetal liver and placenta. At the end of this study, we will produce unique information about human fetal exposure to PBDEs and OH-PBDEs during the second trimester, including empirical relationships between maternal and fetal exposures which can be used to estimate fetal exposures when only maternal levels are available. Further, this will be the first ever in vio data on the relationship between PBDE exposure and human fetal CYP activity. Collectively, this information will help bridge the gap between experimental toxicology and human observation studies and will improve our understanding of population risks to PBDEs as well as other structurally similar environmental chemicals that interact with xenobiotic-sensing nuclear receptors.

描述（由申请人提供）：我们的提案测试了以下假设：多溴二苯醚 (PBDE) 及其代谢物 (OH-PBDE) 在人类胎儿肝脏和胎盘中的积累方式与母体血清中不同，并且胎儿接触 PBDE 会影响胎儿代谢容量。几乎所有美国孕妇都会接触至少一种（通常是多种）PBDE，这是一类持久性有机化学品，自 20 世纪 70 年代以来广泛用作消费品中的阻燃剂。多溴联苯醚是一个重要的公共卫生问题，因为体外和体内研究表明，在子宫内暴露会对胎儿发育产生不利影响。人类暴露和流行病学研究主要通过测量替代生物样本（例如分娩时收集的母血和脐带血）中的化学物质来表征子宫暴露。这些样本不一定代表怀孕早期胎儿的暴露情况，特别是肝脏和胎盘等目标器官的暴露情况。我们建议测量自愿中期妊娠终止的妇女的人类母体和胎儿生物样本中的 PBDE 和 OH-PBDE 水平。由于化学品引起的人类胎儿代谢能力变化的数据对于了解子宫内毒性机制至关重要，但目前缺乏，因此我们还将生成原始人类数据，了解胎儿接触 PBDE 是否会改变胎儿细胞色素 P450 (CYP) 酶的基因表达。妊娠中期人类胎儿肝脏和胎盘。在这项研究结束时，我们将提供有关人类胎儿在妊娠中期接触 PBDE 和 OH-PBDE 的独特信息，包括母体和胎儿接触之间的经验关系，可用于在仅获得母体水平时估计胎儿暴露。此外，这将是有史以来第一个关于 PBDE 暴露与人类胎儿 CYP 活性之间关系的体内数据。总的来说，这些信息将有助于弥合实验毒理学和人类观察研究之间的差距，并将提高我们对多溴二苯醚以及与异生物质感应核受体相互作用的其他结构相似的环境化学物质的人群风险的了解。