Mechanisms of bisphenol A and its analogs as endocrine disruptors via nuclear receptors and related signaling pathways

Abstract Bisphenol A (BPA) is a widely used chemical that is slowly being phased out due to its toxic properties. The industry is therefore looking for alternatives in the form of BPA analogs. However, studies have shown that BPA analogs can have comparable or even stronger endocrine and toxic effects than BPA. This review describes various mechanisms and interactions of BPA analogs with individual nuclear receptors. They interfere with downstream signaling pathways not only by binding to the nuclear receptors, but also by various alternative mechanisms, such as altering receptor expression, affecting co-receptors, altering signal transduction pathways, and even epigenetic changes. Further studies are needed to fully investigate the potential synergistic and additive effects that may result. In the search for a less harmful alternative to BPA, affinity to the nuclear receptor may not be the decisive factor. We therefore recommend a different study approach to assess their effects on the endocrine system before new BPA analogs are introduced to the market to protect public health and the environment.