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.
We will use a human embryonic stem cell system for study effects of BAP on early human develoment. This information will help us identify novel mechanisms that might be play a role in BPA-induced fetal damage. We will use this information to inform prevention related activities at the personal, community and system wide level.
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