Developmental Exposure to Environmental Estrogens Alters Adult Behavior in Female Rodents

Abstract

Humans and wildlife are exposed to numerous anthropogenic drugs and pollutants. Many of these compounds are hormonally active and recent evidence strongly suggests that the presence of these endocrine disruptors can permanently alter normal development and physiology in a variety of vertebrate species. The experiments in this project investigated the effects of two common estrogenic pollutants. Bisphenol a is a monomer of polycarbonate plastic used to make resins for the food and dental industries. Ethinyl estradiol is used pharmaceutically as the active estrogen in the oral contraceptive pill. The majority of past research on these chemicals has focused on reproductive physiology. The focus of my research in on the behavioral consequences of developmental exposure to these compounds. Estrogens will feminize the reproductive system but will masculinize the rodent nervous system, so I focused on identifying whether females would show masculinization of sexually dimorphic traits. The effects of these compounds were studied on two commonly used laboratory species, the mouse (Mus musculus domesticus) and the rat (Rattus norvegicus). The test animals were exposed to environmentally relevant levels of these compounds (ranging from 2 — 200 μg/kg/day for bisphenol A and 0.05 to 50 μg/kg/day for ethinyl estradiol) throughout prenatal and early postnatal development. After this exposure, the animals were allowed to reach adulthood and then observed in a variety tests measuring sexually dimorphic behaviors. These include short-term spatial memory, anxiety, saccharin preference, motor activity and lordosis. Developmental exposure to ethinyl estradiol was found to masculinize every behavior measured in both species in a dose-dependent fashion. Bisphenol A disrupted selected behaviors, namely anxiety and motor activity, and was active in both rodent species, but did not always follow a clear dose response. These results indicate that sexually dimorphic behavior can be exquisitely sensitive to endocrine disruption. In addition, these experiments suggest that both humans and wildlife are presently being exposed to levels of these endocrine disrupting compounds that are sufficient to disrupt the development of the nervous system and that may have permanent consequences on sexually dimorphic behaviors.