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;但对人类的机制知之甚少。我们建议通过使用人类胚胎干细胞（hESC）作为研究BPA对人类胚胎发育影响的体外模型系统来解决我们知识中的这一差距。使用微阵列方法，我们将测量在多个时间点观察到的hESC集落中由环境相关BPA剂量诱导的全局基因表达的变化。我们将用生理相关剂量的17 β-雌二醇（E2）进行平行实验，以了解雌激素依赖性效应的程度。通过识别并验证BPA暴露在蛋白质水平和部分分化的胚状体中改变的特定分子靶点，我们将获得有关BPA诱导干扰人类发育早期事件的机制的重要信息。 在PEEC形成中心，从这些实验中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接触有害化学品的认识。

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.