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

PFBS暴露对不良妊娠结局和胎儿发育的影响 全氟丁烷磺酸盐（PFBS）是一种新型化学品，广泛应用于工业和家用产品， 据报告，该物质具有持久性、生物累积性和毒性。这项建议的科学目的是 基于PFBS的毒性以及我们的初步发现，即接触PFBS可能导致怀孕- 上海地区新生儿妊高征与母儿甲状腺激素水平的关系 (SBC)由我的主要导师Jun Jim Zhang博士领导。妊高征的患病率（~10%）在中国很高， 相关并发症仍然威胁着全球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， 中国，尤其是女性，患甲状腺功能减退症的风险更高（约17%）。固有甲状腺激素 水平对胎儿生长和维持妊娠至关重要。包括PFBS在内的环境暴露可 导致这些不良后果。因此，本提案的主要目的是调查 孕妇暴露于PFBS对妊高征的风险以及孕妇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， 我们将回答关键的和新的流行病学和生物学研究问题。分子生物学 用于研究机制的测定是创新的，特别是全基因组染色质可及性， 这是研究表观遗传学的最新最先进的方法。成功实现这些目标的基础是 我的专业知识（强大的分子生物学培训和母胎医学研究经验）， 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。我将通过与专家合作， 通过正式课程、有指导的结构化培训和实验室工作，在相关领域开展工作。这个项目 我将通过备受推崇的LMIC研究，充分利用上海现有的基础设施 这将使我能够建立一个6500 - 10000名妇女的怀孕队列，并跟踪新生儿的情况。 以成本效益高的方式，最多可达两年。这笔补助金，除了提供必要的培训， 作为一个独立的国际研究人员，将解决有关证据的重要差距， 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。

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.