孕期双酚类暴露、胎盘mtDNA与同卵双胎出生结局差异的关联研究

双酚A及其替代物（简称双酚类物质，bisphenol contaminates，BPCs）是一类环境介质中普遍存在的化学污染物，毒理学研究明确表明其具有发育毒性，并可造成胎盘线粒体DNA损伤。同卵双胎相对于单胎对外界化学物质暴露具有更高的易感性，孕期暴露BPCs更易造成同卵双胎宫内生长不利。本项目以武汉市妇女与儿童医疗保健中心为研究现场，采用前瞻性队列研究设计，拟通过综合评估孕妇孕早、中和晚期尿样中BPCs的暴露水平，分析孕妇不同孕期暴露水平对同卵双胎出生结局差异的影响，揭示暴露敏感窗口期。在此基础上，通过分析胎盘线粒体DNA含量，作为反映胎盘对外环境暴露引起氧化损伤的敏感分子指标，探究其在孕妇BPCs与同卵双胎出生结局差异中的中介作用。研究结果将为BPCs的生殖健康风险评估及潜在作用机制提供基于同卵双胎的科学依据。

Bisphenol A (BPA) and its substitutes (namely bisphenol contaminates, BPCs) are ubiquitous chemical contaminants in environment. Toxicological studies have shown that they are developmentally toxic and can damage placental mitochondrial DNA. Compared with singletons, monozygotic twins have a higher susceptibility to external chemical exposure. Exposure to BPCs during pregnancy is more likely to cause adverse intrauterine growth in monozygotic twins. We designed a prospective cohort study to comprehensively evaluate exposure levels of maternal urine BPCs during early, mid-, and late pregnancy at Wuhan Women and Children Medical Care Center. Further, we will examine associations between the exposure levels of pregnant women during different periods of gestation and discordant birth outcomes of monozygotic twins, and identify the sensitive windows of exposure. On this basis, we will analyze mitochondrial DNA content of placenta, as a sensitive molecular biomarker, to reflect the oxidative damage caused by exposure to external environment of placenta and to explore the mediation effect of maternal BPC exposure on discordance birth outcomes of monozygotic twins. The results of the project will provide a scientific basis for reproductive health risk estimation and potential mechanism of BPCs in monozygotic twins.