Unraveling molecular targets of bisphenol A and S in the thyroid gland

Bisphenol A (BPA) is a well-known endocrine disruptor with several effects on reproduction, development, and cancer incidence, and it is highly used in the plastic industry. Bisphenol S (BPS) was proposed as an alternative to BPA since it has a similar structure and can be used to manufacture the same products. Some reports show that BPA interferes with thyroid function, but little is known about the involvement of BPS in thyroid function or how these molecules could possibly modulate at the same time the principal genes involved in thyroid physiology. Thus, the aims of this work were to evaluate in silico the possible interactions of BPA and BPS with the thyroid transcription factors Pax 8 and TTF1 and to study the actions in vivo of these compounds in zebrafish thyroid gene expression. Adult zebrafish treated with BPA or BPS showed that sodium iodide symporter, thyroglobulin, and thyroperoxidase genes were negatively or positively regulated, depending on the dose of the exposure. Human Pax 8 alignment with zebrafish Pax 8 and Rattus norvegicus TTF1 alignment with zebrafish TTF1 displayed highly conserved regions in the DNA binding sites. Molecular docking revealed the in silico interactions between the protein targets Pax 8 and TTF1 with BPA and BPS. Importance of some amino acids residues is highlighted and ratified by literature. There were no differences between the mean energy values for BPA docking in Pax 8 or TTF1. However, BPS energy values were lower in TTF1 docking compared to Pax 8 values. The number of amino acids on the protein interface was important for Pax 8 but not for TTF1. The main BPA interactions with proteins occurred through Van der Waals forces and pi-alkyl and alkyl interactions, while BPS interactions mainly occurred through carbon hydrogen bonds and conventional hydrogen bonds in addition to Van der Waals forces and pi-alkyl interactions. These data point to a possible interaction of BPA and BPS with Pax 8 and TTF1.