A large and growing base of science demonstrates that exposure to chemicals that can alter the function of the endocrine system during specific periods of fetal development can result in health consequences that manifest in childhood and adulthood, for example, cancer, cardiovascular effects and diabetes. The latter connection has evolved into the fetal origin of adult disease hypothesis. Large national biomonitoring studies are reporting nearly ubiquitous exposure to numerous environmental contaminants in the US population - bisphenol A, phthalates, octylphenols, polybrominated diphenol ethers, perchlorate - raising the question of how people are being exposed. Furthermore, studies of mid-gestation fetal exposure confirm that the placenta does not act as a barrier to exogenous chemicals and also indicate that the fetus may experience higher levels of exposure than the mother. Thus, human fetal exposure to chemicals represents a previously unexplored, yet critical public health question. We propose to measure levels of exposure to the chemical Bisphenol A, a chemical shown to increase risk of adverse affects from fetal exposures, in maternal and fetal biological specimens from women undergoing elective pregnancy terminations between 14 and 23 weeks gestation, including maternal serum and urine, amniotic fluid, umbilical cord blood, and placenta. We will also develop and implement a questionnaire about potential sources of exposure to this widely used chemical and will provide original data on fetal hepatic metabolism of BPA and the role of specific hepatic glucuronidation enzymes in catalyzing BPA metabolism. This project will provide significant and unprecedented insights into maternal and human fetal exposures to BPA, including data that can be used to predict fetal exposures to environmental contaminants based solely on levels in maternal biological samples, such as urine or blood, which are the less invasive to collect. We will also contribute unique exposure assessment data that links information on contact with sources of exposure to actual levels measured in biological samples. The combined data from this study will set the stage for subsequent studies to explore the effects of BPA on the development of specific organ systems. In addition, with the successful implementation of this pilot study, we will be poised to rapidly broaden our studies to explore the exposures and effects of other environmental contaminants.

Public Health Relevance

The results of this study will substantially advance our understanding of human maternal and fetal exposures to Bisphenol A, including sources and predictors of exposure and hepatic metabolic transformation. Insights gained about the sources of exposure and the role of fetal metabolic phase II metabolism will be applicable to other environmental chemicals that have similar sources of exposure and are detoxified through the same pathways.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Exploratory/Developmental Grants (R21)
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Xenobiotic and Nutrient Disposition and Action Study Section (XNDA)
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Heindel, Jerrold
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University of California San Francisco
Obstetrics & Gynecology
Schools of Medicine
San Francisco
United States
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Vandenberg, Laura N; Gerona, Roy R; Kannan, Kurunthachalam et al. (2014) A round robin approach to the analysis of bisphenol A (BPA) in human blood samples. Environ Health 13:25
Gerona, Roy R; Woodruff, Tracey J; Dickenson, Carrie A et al. (2013) Bisphenol-A (BPA), BPA glucuronide, and BPA sulfate in midgestation umbilical cord serum in a northern and central California population. Environ Sci Technol 47:12477-85