Environmental Factors and Their Role in Developmental Disorders

From conception to death exposure to environmental agents with potential toxicity is unavoidable. Advancement of the chemical industry in the 20th century has led to an estimated 70,000 to 100,000 chemicals registered for commercial use, the majority of which have had little to no toxicological testing. Further 90% of approved pharmacological drug treatments in the U.S. have no evaluation of teratogenicity or neurodevelopmental toxicity in humans. This gap in our knowledge of exposure to these chemicals and their toxicological potential is significant reason for concern. In the present study, two potential neurodevelopmental toxicants, brominated diphenyl ether-47 (BDE-47), an environmental pollutant, and misoprostol, a pharmacological agent, were evaluated for effects on brain development and behavior in mice after early developmental exposure.;BDE-47 is one of 209 congeners in a class of widely used flame retardant chemicals known as polybrominated diphenyl ethers (PBDEs). BDE-47 makes up almost 50% of the congener profile in human tissues including breast milk, placenta and umbilical cord serum. To evaluate the neurotoxic potential of BDE-47, mice were chronically exposed low levels of BDE-47 (i.e., 0.03, 0.1 or 1.0 mg/kg/day) that were selected to be within the range of reported human exposure. Our research found that exposure of pregnant C567BL/6 dams to BDE-47 resulted in significant accumulation of the chemical in offspring tissue both during gestation and lactation, and levels in dam tissues were similar to those reported for humans. Behavioral testing showed that spatial learning and memory were altered in mouse pups following perinatal exposure. These results highlight the potential health risk that presented by perinatal exposure to BDE-47 and potentially other similar flame retardants.;Misoprostol is commonly used in gynecological and obstetric practices at the time of birth to induce labor. However, high doses of misoprostol given early in pregnancy to induce abortion can result in Möbius Syndrome in surviving offspring as well as behaviors that show similarities with autism spectrum disorders. This raised the possibility that misoprostol treatment might show neurodevelopmental toxicity when given at the time of birth. Therefore mouse pups were exposed to one of three doses of misoprostol (0.4, 4or 40 mg/kg) at the approximate time in development equivalent to human birth. The results showed that when misoprostol is given at this developmental age it did not appear to significantly affect neurological development in mice. This failure to find evidence of neurodevelopmental toxicity from neonatal exposure to misoprostol is important because it can help future research to focus on those environmental agents that may be more likely to be involved in the etiology of neurodevelopmental disorders such as autism.