Abstract
Neurodevelopmental disorders (NDDs) are a complex group of conditions that currently impact about one in six individuals in the United States. Genetic and environmental factors both contribute to the complex etiologies of NDDs; however, it is not well understood how an individual’s genetic susceptibilities and specific environmental factors may converge to contribute to the onset of NDDs. One such environmental factor is a group of chemicals called bisphenols. Bisphenols are used to produce polycarbonate plastics and epoxy resins and are found in numerous commercial products. The most well-known bisphenol—bisphenol A (BPA)—is well-established as an endocrine disrupting chemical, but more recent studies have also linked BPA exposure to abnormal neurodevelopment in several model organisms. Due to its established harmful effects, BPA has been removed from some commercial products; but manufacturers often replace BPA with chemical analogues, like bisphenol F (BPF), that have undergone far less toxicological testing than BPA. Due to its similarity with BPA, BPF may have similar harmful effects. This project aimed to determine how BPF affected neurodevelopment on its own or in combination with fragile X mental retardation 1 (FMR1)—a gene that is associated with multiple NDDs—using Drosophila melanogaster as a model. Fruit flies possess a functional ortholog of human FMR1 called Drosophila fragile X mental retardation 1 (fmr1), and loss of fmr1 disrupts a number of behavioral and neuronal processes. We exposed two wild-type strains (Canton-S and w1118) and fmr1 null mutant flies to 1 millimolar (mM) and 2 mM BPF throughout development and then assessed naïve courtship behaviors, axon pathfinding, and developmental lethality. BPF caused a significant decrease in the courtship index of w1118 flies, but not Canton-S or fmr1 mutant flies. When we assessed axon pathfinding phenotypes, we observed that BPF did not impact Canton-S or w1118 flies. Interestingly, exposure to BPF caused a rescue effect by decreasing the frequency of axon pathfinding defects in the fmr1 mutant genetic background. Finally, BPF caused developmental lethality in w1118 flies, but not Canton-S or fmr1 mutant flies. Overall, our results indicate that developmental exposure to BPF: (1) does not impact Canton-S flies, (2) causes detrimental effects in w1118 flies, and (3) either had no effect or a neuroprotective effect in the fmr1 mutant genetic background. These results highlight the importance of performing toxicological assessment in distinct genetic backgrounds.