Effects of Bisphenol A and Retinoic Acid Exposure on Neuron and Brain Formation: A Study in Human Induced Pluripotent Stem Cells and Zebrafish Embryos

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BACKGROUND: Developing human fetuses may be exposed to the chemical compound bisphenol A (BPA), and retinoic acid (RA) has been detected at low levels in water sources. RA signaling regulates key developmental genes and is essential for organ development, including the brain. We previously reported that RA/BPA coexposure of mouse embryonic stem cells potentiates RA signaling, which warrants further investigation. OBJECTIVE: gene expression and exert pleiotropic effects on RA signaling. METHODS: hybridization. Mauthner cell and craniofacial cartilage anomalies were studied by immunostaining and Alcian blue staining, respectively. Transcriptome was compared between iPSCs and zebrafish to identify alterations of common biological processes. Gradient curves of RA signal were calculated to simulate the effects of exogenous RA and BPA in zebrafish. RESULTS: expression and increased rate of anomalies in Mauthner cells and craniofacial cartilage. Transcriptome comparison and correlations between the experimental results and gradient curve simulations strengthened these observations. CONCLUSION: Our findings suggest a mechanistic link between chemical exposure and neurodevelopmental impairments and demonstrate involvement of exogenous RA signaling in endocrine disruption. Further investigation is needed to explore why BPA alone did not affect endogenous RA signaling, whereas exogenous RA signaling was potentiated with RA/BPA coexposure. https://doi.org/10.1289/EHP15574.

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