Bisphenol F affects neurodevelopmental gene expression, mushroom body development, and behavior in Drosophila melanogaster.

Bisphenol F (BPF) is a potential neurotoxicant used as a replacement for bisphenol A (BPA) in polycarbonate plastics and epoxy resins. We investigated the neurodevelopmental impacts of BPF exposure using Drosophila melanogaster as a model. Our transcriptomic analysis indicated that developmental exposure to BPF caused the downregulation of neurodevelopmentally relevant genes, including those associated with synapse formation and neuronal projection. To investigate the functional outcome of BPF exposure, we evaluated neurodevelopmental impacts across two genetic strains of Drosophila- w1118 (control) and the Fragile X Syndrome (FXS) model-by examining both behavioral and neuronal phenotypes. We found that BPF exposure in w1118 Drosophila caused hypoactive larval locomotor activity, decreased time spent grooming by adults, reduced courtship activity, and increased the severity but not frequency of ß-lobe midline crossing defects by axons in the mushroom body. In contrast, although BPF reduced peristaltic contractions in FXS larvae, it had no impact on other larval locomotor phenotypes, grooming activity, or courtship activity. Strikingly, BPF exposure reduced both the severity and frequency of ß-lobe midline crossing defects in the mushroom body of FXS flies, a phenotype previously observed in FXS flies exposed to BPA. This data indicates that BPF can affect neurodevelopment and its impacts vary depending on genetic background. Further, BPF may elicit a gene-environment interaction with Drosophila fragile X messenger ribonucleoprotein 1 (dFmr1)-the ortholog of human FMR1, which causes fragile X syndrome and is the most common monogenetic cause of intellectual disability and autism spectrum disorder.

Bisphenol a affects neurodevelopmental gene expression, cognitive function, and neuromuscular synaptic morphology in Drosophila melanogaster.

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.