Endocrine disrupting chemicals (EDC) are pollutants that disturb normal functioning of the endocrine system. Exposure to such pollutants during pre-natal development can have detrimental effects on the developing fetus because the system is highly plastic and responsive during critical periods. There has been much concern recently about the action of these pollutants on fetuses in utero. One such compound that is prevalent in the environment is bisphenol A (BPA). It is used to make polycarbonate bottles, including baby bottles and linings of cans, so exposure is widespread. Studies in rodents have implicated prenatal BPA exposure in a variety of health problems. We propose to use sheep as a model to examine the effects of prenatal BPA on complex behaviors. Similar work with prenatal testosterone exposure has demonstrated that sheep are an excellent model for such studies. Studies at our facility using sheep as a model for prenatal BPA exposure indicate that exposure to BPA leads to reproductive disruptions. However, no work has yet been done to examine the lifespan development of complex behaviors in a long-lived social species, such as ourselves. The goal of this study is to investigate the effects of prenatal BPA exposure and adolescent BPA exposure on complex behaviors in the sheep model across development. These behaviors will be correlated with physiological endpoints including steroid hormone levels, stress reactivity and body weight. Additionally, we will be examining steroid receptor number and distribution in areas of the brain associated with motivation and consummation of mating behavior. We hypothesize that prenatal exposure to BPA, at levels similar to the exposure of human fetuses, will disrupt a variety of complex behaviors including play, aggressive, motivational and sex behaviors over the lifespan of the animal. A second period of vulnerability is adolescence, so we will also examine the effects of BPA exposure during adolescence.
Specific Aims 1 and 2 will examine complex behaviors throughout the lifespan of both male and female exposed to either prenatal, adolescent or prenatal and adolescent BPA compared to controls.
Specific Aim 3 will examine the effect of BPA exposure during these vulnerable periods on steroid receptor number and distribution in areas of the brain associated with motivation and consummation of mating behavior. Results from this study are important for characterizing the behavioral and developmental effects of prenatal exposure to the endocrine disruptor BPA. This is an important issue in society, since many products that mothers and young children are exposed to contain BPA.

Public Health Relevance

Bisphenol A (BPA), an endocrine disrupting chemical, is widely used in the industrialized world. Of particular concern is the effect during critical periods of reproductive development, including in utero and adolescent exposure to BPA, which can have detrimental physiological and behavioral effects. This project will examine the behavioral and neurochemical effects of prenatal BPA exposure in the sheep model.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Integrative and Clinical Endocrinology and Reproduction Study Section (ICER)
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Heindel, Jerrold
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University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
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