Prenatal Exposure to PBDE47 Alters Motor Behaviors and Spatial Learning in C57BL/6J Mice

Background: Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants found in a variety of products from carpeting to plastics. These compounds are accumulating in the environment and have become persistent world-wide contaminants for human and animal populations. This is of concern because PBDEs, and PBDE47 in particular, can contaminate the fetus by crossing the placental barrier or through breast milk. Therefore, these compounds may represent a serious risk to the developing fetus. Objectives: To examine the effects of low level, chronic, perinatal exposure to PBDE47 on brain development and behavior in C57BL/6J mice. Methods: Female mice were fed one of three doses of PBDE47 (0.03, 0.10 or 1.0 mg/kg/day) or vehicle beginning 4 weeks before mating, throughout gestation, and over the preweaning period for a total of 70 days exposure. Levels of PBDE47 were measured in brain and other tissues of exposed dams and their offspring. Offspring were tested for sensory, motor and cognitive function, and their brains were examined for evidence of neuronal loss using stereological procedures. Results: Dose related elevations of tissue levels of PBDE47 were found in blood, brain, adipose tissue of dams that increased over the course of exposure. Offspring also showed substantial levels of PBDE47 present in their blood and brain when measured on postnatal days 1, 14 and 21. Offspring exposed to PBDE47 at a dose of 0.10 mg/kg/day showed reduced somatic growth over postnatal days 8-18. Behavioral testing of offspring revealed significant motor impairments and altered spatial memory performance. No significant loss of neurons was found in the brains of exposed offspring. Conclusions: Exposure of pregnant dams to PBDE47 results in significant exposure of their offspring, with tissue levels in brain approaching that of the dams. Exposure delayed somatic growth, impaired motor development and resulted in abnormal memory performance. These data demonstrate that perinatal exposure to PBDE47 at low, physiologically relevant levels can alter the normal course of growth and development.