Bisphenol A (BPA) is an environmentally prevalent endocrine disrupting chemical that can impact human health and may be an environmental risk factor for neurodevelopmental disorders. BPA has been associated with behavioral impairment in children and a variety of neurodevelopmental phenotypes in model organisms. We used Drosophila melanogaster to explore the consequences of developmental BPA exposure on gene expression, cognitive function, and synapse development. Our transcriptome analysis indicated neurodevelopmentally relevant genes were predominantly downregulated by BPA. Among the misregulated genes were those with roles in learning, memory, and synapse development, as well as orthologs of human genes associated with neurodevelopmental and neuropsychiatric disorders. To examine how gene expression data corresponded to behavioral and cellular phenotypes, we first used a predator-response behavioral paradigm and found that BPA disrupts visual perception. Further analysis using conditioned courtship suppression showed that BPA impairs associative learning. Finally, we examined synapse morphology within the larval neuromuscular junction and found that BPA significantly increased the number of axonal branches. Given that our findings align with studies of BPA in mammalian model organisms, this data indicates that BPA impairs neurodevelopmental pathways that are functionally conserved from invertebrates to mammals. Further, because Drosophila do not possess classic estrogen receptors or estrogen, this research suggests that BPA can impact neurodevelopment by molecular mechanisms distinct from its role as an estrogen mimic.
5 SC2 GM132005
National Science Foundation
Behavior, Bisphenol A, Drosophila melanogaster, RNA-sequencing, Synaptogenesis
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Chloe Welch, Eden Johnson, Angelina Tupikova, Judith Anderson, Brendan Tinsley, Johnathan Newman, Erin Widman, Adam Alfareh, Alexandra Davis, Lucero Rodriguez, Clayton Visger, Justin P. Miller-Schulze, Wendy Lee, and Kimberly Mulligan. "Bisphenol a affects neurodevelopmental gene expression, cognitive function, and neuromuscular synaptic morphology in Drosophila melanogaster" NeuroToxicology (2022): 67-78. https://doi.org/10.1016/j.neuro.2022.01.006