Combined Exposure to BPA and Retinoic Acid Can Impair Brain Development by Altering Gene Expression

Recent research indicates that exposure to bisphenol A (BPA), a chemical widely used in plastics, together with retinoic acid (RA), a vital nutrient for organ development, can cause significant disruptions in early brain development. The study, conducted by Professor Tatsuyuki Takada of Ritsumeikan University and colleagues from Kyoto University, explores how these substances interact, particularly focusing on their impact on gene expression related to neural and facial development.

BPA is known to act as an endocrine disruptor, affecting hormonal receptors such as estrogen, androgen, and thyroid receptors, which can lead to reproductive, immune, and neuroendocrine health issues. However, its mechanisms in affecting neurodevelopment were not thoroughly understood. Since low levels of RA are also found in water sources, researchers aimed to investigate the combined impact of BPA and RA.

The study involved exposing human induced pluripotent stem cells (iPSCs) and zebrafish embryos to BPA and RA, both separately and in combination. The results showed that co-exposure significantly overstimulated RA-responsive genes, especially HOX genes, which are critical in body patterning during development. This overstimulation was linked to abnormal brain and facial formation, including brain region shifts (such as increased hoxb1a gene activity), neuron duplication, and craniofacial deformities.

According to Professor Takada, "When cells were exposed to BPA and RA together, BPA enhanced RA signaling far beyond normal levels, resulting in developmental anomalies". Interestingly, BPA alone did not produce effects, but combined with RA, it caused dramatic changes in gene expression and brain structure—effects that were mitigated by blocking RA receptors, confirming BPA’s action through these pathways.

The zebrafish model exhibited various neurodevelopmental abnormalities, including duplicated neurons and facial malformations. These findings raise concerns about potential links between chemical exposure during pregnancy and neurodevelopmental disorders like autism spectrum disorder and ADHD.

The relevance of this research is heightened by the detection of RA-like activity in drinking water and the persistent presence of BPA in household products. The researchers advocate for stricter environmental policies and further research into how chemical and nutrient interactions influence human health. They also highlight the importance of understanding how simultaneous exposures could increase risks for developing fetuses and pregnant women, given RA’s crucial role in development.

This study emphasizes the complex ways endocrine-disrupting chemicals interfere with biological pathways and underscores the need for comprehensive monitoring and regulation to protect vulnerable populations from subtle yet profound developmental disruptions.