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

全氟辛烷磺酸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)是一种广泛应用于工业和家居产品的新型化学品。 持久性、生物蓄积性和毒性特性已有报道。这项提议的科学目标是 基于全氟辛烷磺酸的毒性和我们的初步研究结果，暴露于全氟辛烷磺酸会导致怀孕- 上海出生队列中妊娠高血压与母婴甲状腺激素水平的变化 (SBC)由我的主要导师张军博士领导。妊娠高血压综合征的患病率(~10%)在中国和妊高征患者中较高。 相关并发症仍在威胁着全世界的孕产妇和胎儿的生命和健康，因为缺乏 有效的治疗方法。流行病学研究指出，甲状腺相关疾病在#年爆发。 中国，尤其是女性，患甲状腺功能减退症的风险更高(~17%)。适当的甲状腺激素 这一水平对胎儿生长和维持妊娠至关重要。包括全氟苯并苯的环境暴露可能 造成这些不利后果。因此，这项建议的主要目的是调查 孕妇暴露于全氟辛烷磺酸对妊高征发病风险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基本机制。一项关键的创新是 我们将回答关键和新的流行病学和生物学研究问题。分子生物学 研究机制的分析方法是创新的，特别是全基因组染色质的可及性，这是一种 研究表观遗传学的最新和最先进的方法。成功实现这些目标的基础是 我的专长(在母体胎儿医学方面有很强的分子生物学培训和研究经验)和 将其扩展到全球研究环境中的暴露评估和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获得必要的专业知识 相关领域通过正式的课程工作、有组织的指导培训和实验室工作。这个项目 将通过备受推崇的LMIC研究，利用上海现有的基础设施 该机构将使我能够建立一个由6,500-10,000名妇女组成的怀孕队列，并跟踪新生儿 最多两年，以具有成本效益和效率的方式。这笔赠款，除了为我提供必要的培训外 将被确立为独立的国际研究人员，将解决关于 暴露于全氟辛烷基苯对孕产妇和儿童健康的影响，并将为今后的研究提供资源。

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.