Effects of perfluorobutane sulfonate (PFBS) exposure on adverse pregnancy outcomes and fetal development

全氟丁磺酸 (PFBS) 暴露对不良妊娠结局和胎儿发育的影响

基本信息

批准号：
9925851
负责人：
Liping Feng
金额：
$ 10.61万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9925851
关键词：
Address Affect Air Alkanesulfonates Biological Biological Assay Birth Case-Control Studies Cell physiology Cells Chemicals Child China Chromatin Cities Country Data Developed Countries Developing Countries Development Development Plans Diet Disease Outbreaks Dust Economic Development Endocrine Enrollment Environment Environmental Exposure Environmental Health Environmental Pollutants Environmental Pollution Epigenetic Process Exposure to Female Fetal Development Fetal Growth Fetal health Foundations Functional disorder Future Genetic Transcription Goals Government Agencies Grant Growth Health Health Personnel Health Policy High Risk Woman Household Household Products Human Hypothyroidism Industrial Product Industrialization Industry Infrastructure Institution Interdisciplinary Study International Investigation Knowledge Laboratories Lead Life Link Maintenance Malignant Neoplasms Manufacturer Name Maternal Exposure Maternal Health Maternal and Child Health Maternal-fetal medicine Mentors Mentorship Methods Modification Molecular Biology Morbidity - disease rate Mothers Mus Newborn Infant Outcome Pathway interactions Perinatal Epidemiology Perinatal Exposure Phase Pilot Projects Placenta Policies Positioning Attribute Pregnancy Pregnant Women Prevalence Production Property Public Health Regulation Reporting Research Research Design Research Personnel Resources Risk Risk Factors Scientist Soil Structure Surface Therapeutic Thyroid Gland Thyroid Hormones Thyrotropin Thyroxine Time Toxic effect Training Umbilical Cord Blood Vulnerable Populations Water Woman Work adverse outcome adverse pregnancy outcome base bioaccumulation biological research career career development cohort cost cost effective cytotrophoblast design didactic education drinking water epidemiology study experience exposed human population fetal genome-wide global health immunoregulation improved innovation low and middle-income countries mortality multidisciplinary novel pregnancy hypertension pregnant programs prospective recruit reproductive reproductive development reproductive epidemiology sample collection trend trophoblast water solubility

项目摘要

Effects of PFBS exposure on adverse pregnancy outcomes and fetal development. Perfluorobutane sulfonate (PFBS) is a new chemical widely used in industrial and household products and its persistence, bioaccumulation and toxic properties has been reported. The scientific aims of this proposal are based on the toxicity of PFBS and our preliminary findings that exposure to PFBS can lead to pregnancy- induced hypertension (PIH) and altered maternal and fetal thyroid hormone levels in a Shanghai Birth Cohort (SBC) led by my primary mentor, Dr. Jun Jim Zhang. The prevalence of PIH (~10%) is high in China and PIH- related complications are still threatening maternal and fetal life and health worldwide due to the lack of efficient therapeutic methods. Epidemiology studies have pointed to a thyroid-related disease outbreak in China, especially women are at higher risk of developing hypothyroidism (~17%). Proper thyroid hormone levels are critical for fetal growth and maintaining pregnancy. Environmental exposures including PFBS can contribute to these adverse outcomes. Therefore, the major aim of this proposal is to investigate the effect of maternal exposure to PFBS on the risk of PIH and maternal and cord blood levels of thyroid hormones in Shanghai. We also propose to investigate the underline mechanisms of these findings. A key innovation is that we will answer critical and novel epidemiological and biological research questions. The molecular biology assays for studying mechanisms are innovative, especially the genome-wide chromatin accessibility which is a novel and the most advanced approach to study epigenetics. Successful completion of these aims builds on my expertise (strong molecular biology training and research experiences in maternal fetal medicine) and extends it to exposure assessment and reproductive and perinatal epidemiology in a global research setting that requires additional training and mentorship. I will attain the necessary expertise by working with experts in the relevant fields, through formal course work, structured mentored training and laboratory work. This project will take advantage of the available infrastructure in Shanghai through the highly respected LMIC research institution that will enable me to establish a pregnancy cohort of 6,500-10,000 women and follow the newborns up to two years at a cost effective efficient manner. This grant, beyond providing the necessary training to me to be established as an independent international researcher, will address important gaps in evidence on the effects of PFBS exposure on maternal and child health, and will provide a resource for future studies.

PFBS 暴露对不良妊娠结局和胎儿发育的影响。全氟丁烷磺酸（PFBS）是一种广泛应用于工业和家用产品的新型化学品，其持久性、生物蓄积性和毒性已有报道。该提案的科学目标是根据 PFBS 的毒性以及我们的初步发现，接触 PFBS 可能导致怀孕- 上海出生队列中诱发性高血压（PIH）和母婴甲状腺激素水平的改变（SBC）由我的主要导师张军博士领导。中国 PIH 的患病率很高（约 10%），并且 PIH- 由于缺乏足够的治疗手段，相关并发症仍然威胁着全世界孕产妇和胎儿的生命和健康。有效的治疗方法。流行病学研究指出，甲状腺相关疾病在中国，尤其是女性，患甲状腺功能减退症的风险较高（~17%）。适当的甲状腺激素水平对于胎儿生长和维持妊娠至关重要。包括 PFBS 在内的环境暴露可助长了这些不良后果。因此，本提案的主要目的是研究母亲接触 PFBS 对 PIH 风险以及母亲和脐带血甲状腺激素水平的影响上海。我们还建议调查这些发现的潜在机制。一个关键的创新是我们将回答关键和新颖的流行病学和生物学研究问题。分子生物学研究机制的测定是创新的，特别是全基因组染色质可及性，这是一个研究表观遗传学的新颖且最先进的方法。成功完成这些目标的基础是我的专业知识（母胎医学方面强大的分子生物学培训和研究经验）以及将其扩展到全球研究环境中的暴露评估以及生殖和围产期流行病学这需要额外的培训和指导。我将通过与以下领域的专家合作获得必要的专业知识通过正式课程、结构化指导培训和实验室工作，深入了解相关领域。这个项目将通过备受推崇的中低收入国家研究，利用上海现有的基础设施使我能够建立一个由 6,500-10,000 名妇女组成的妊娠队列并跟踪新生儿的机构以具有成本效益的高效方式长达两年。这笔赠款不仅为我提供了必要的培训将被建立为一个独立的国际研究员，将解决有关证据的重要空白 PFBS 暴露对孕产妇和儿童健康的影响，并将为未来的研究提供资源。