Project 2: Assessing the Effects on BPA Exposure on Early Human Development

项目总结(见说明)： 在动物研究中，双酚A(BPA)通过多种途径对发育产生不利影响，但对人类的作用机制知之甚少。我们建议通过使用人类胚胎干细胞(HESCs)作为体外模型系统来研究双酚A对人类胚胎发育的影响，利用微阵列方法，我们将测量在多个时间点观察到的环境相关双酚A剂量在hESC群体中诱导的全球基因表达的变化，以解决这一知识缺口。我们将进行一项与生理相关剂量的17β-雌二醇(E2)的平行实验，以了解雌激素依赖的影响程度。通过在蛋白质水平和部分分化的类胚体中鉴定和验证BPA暴露改变的特定分子靶点，我们将获得关于BPA诱导干扰人类发育最早事件的重要机制的重要信息。 在PEEC形成中心内，这些实验产生的信息将用于指导中期妊娠胎儿组织的采样和分析。此外，这些信息将用于针对社区团体、临床医生和患者的教程，旨在教育和提高对预防怀孕期间有害化学物质暴露的认识。

PROJECT SUMMARY (See instructions): In animal studies, Bisphenol A (BPA) adversely impacts development through multiple pathways; yet little is known about mechanisms in humans. We propose to address this gap in our knowledge by using human embryonic stem cells (hESCs) as an in vitro model system for studying the effects of BPA on human embryonic development Using a microarray approach, we will measure changes in global gene expression induced by environmentally-relevant BPA doses in a hESC colony observed over multiple time points. We will conduct a parallel experiment with physiologically-relevant doses of 17beta-estradiol (E2) to understand to what degree effects are estrogen-dependent. By identifying and then validating the specific molecular targets altered by BPA exposure at the protein level and in partially-differentiated embryoid bodies, we will gain important information about the mechanisms that underlie BPA induced interference with the earliest events in human development. Within the PEEC Formative Center, the information generated from these experiments will be used to direct the sampling and analysis of second trimester fetal tissues. Additionally, this information will be used in a tutorial targeted to community groups, clinicians and patients intended to educate and raise awareness on the prevention of harmful chemical exposures in the during pregnancy.