Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with both genetic and environmental etiologies. One class of environmental factors linked to ASD is environmental chemicals. There are over 80,000 chemicals in the Environmental Protection Agency’s registry—many of which have not been adequately assessed for their ability to impact neurodevelopment. Among these chemicals is bisphenol-A (BPA), a high-production, ubiquitous environmental chemical commonly found in plastic bottles, thermal papers and epoxy resins. BPA possesses endocrine-disrupting abilities and has more recently been linked to impaired neurodevelopment in rodents and behavioral differences in children. The goal of this project was to investigate how BPA impacts neurodevelopmental phenotypes in two different genetic backgrounds of Drosophila melanogaster—wild-type Drosophila and Drosophila with a mutation in fragile X mental retardation 1 (Fmr1), a risk gene for ASD in humans. After exposing developing flies to 0, 0.1 or 1 millimolar BPA, we measured larval and adult behaviors, including courtship, larval locomotion and grooming. In the courtship and grooming assays, we specifically analyzed the behavior of adult males. For the larval locomotion assay, we examined a mixed population of male and female larvae. BPA significantly impaired all of these behaviors in wild-type flies, but demonstrated either non-significant or opposite effects in Fmr1 mutant flies. Next, we quantified neural stem cell proliferation (NSC) in the larval brain using immunofluorescence and confocal microscopy to determine the impacts of BPA at the cellular level. For this assay, we examined a mixed population of male and female larvae. BPA exposure did not lead to a significant difference in NSC proliferation in wild-type larvae. However, BPA decreased the rate of NSC proliferation in Fmr1 flies, which normally have elevated NSC proliferation. Our results indicate that BPA affects neurodevelopment, but has differential impacts according to the genetic background.