Effects of Bisphenol A (BPA) on Asthma Pathogenesis

Principal Investigator: Terumi Midoro-Horiuti, MD, PhD

Co-investigators: Randal Goldblum, Cheryl Watson, Bhupendra Kaphalia, George Saade

This project will focus on the important topic of environmental contributions to childhood asthma.This project focuses on the important topic of a potential new environmental contributor to the epidemic of childhood asthma. The long-term goal of our research is to elucidate the role of environmental estrogens, such as bisphenol A (BPA), in the development of asthma and other allergic diseases.

The prevalence of asthma, particularly in children in industrialized countries has increased dramatically over the last 2-3 decades and is now the most common chronic disease of children in the U.S. Given the magnitude of the problem of childhood asthma and the evidence that asthma at any age usually has its genesis in childhood, the impact of our current studies on this public health issue is likely to be very large. We have recently found in an animal model that perinatal exposure to BPA enhances the development of asthma.

Our subsequent studies (submitted for publication) indicate that prenatal, but not early postnatal exposure to BPA was required to produce this effect in the mouse model. We also found that the developmental expression of a hepatic UDP-glucuronyl transferase, that is thought to be responsible for metabolism of BPA, is extremely low in the mouse fetus, but increased rapidly after birth. This is likely a factor in the sensitivity of the fetus to BPA exposures.

Lab WorkThe next phase of this project will rapidly expand ongoing efforts on two campuses, to test the hypothesis that exposure to BPA in utero induces epigenetic changes that alter the early immunologic development that underlies asthma and other common allergic diseases. We plan to use the funding from this pilot project to continue translating our findings from the mouse model to humans, by investigating the effects of prenatal BPA exposure on epigenetic alterations and the function of cord blood mononuclear cells. During the previous cycle, we have recruited 59 mother-newborn pairs. Funds from this project are required to maintain periodic clinical assessments of these subjects and to test the stored sera and mononuclear cell samples for biomarkers of BPA exposure and immunologic precursors of asthma.

Given the short duration of the pilot project, our single specific aim will be to answer the question: Which of the biomarkers of fetal exposure of BPA relate to the propensity to develop asthma? Our results will form the basis for future studies to examine the relationship between selected biomarkers and the prevalence of asthma in an expanded cohort study. These studies will be a strong basis for extramural funding to continue these multidisciplinary and collaborative efforts. These studies should help to inform public health policies for preventing future toxic exposures of BPA.