ORF19-01 - Bisphenol A, and Alternative Bisphenols S, F, Increase Proliferation and Growth of Thyroid Follicular Epithelial Cells and Disrupt Thyroid Histology

Bisphenol A (BPA) is an endocrine-disrupting chemical that is widely used in the production of polycarbonate plastics and epoxy resins. Studies have shown that exposure to BPA can potentially lead to health problems such as reproductive, developmental, and metabolic disorders. Public knowledge of these risks of BPA has led consumers to shift to preferentially buying products which are ‘BPA-free’. However, many products which are advertised as ‘BPA-free’ still contain other bisphenol compounds, such as bisphenol S (BPS) and bisphenol F (BPF). Despite the widespread use of these BPA substitutes, the biologic impact of BPS and BPF exposure remains critically understudied. In this work, we assess the effect of these three bisphenol compounds on the thyroid. A CellTiter-Glo cell viability assay was performed with a human thyroid follicular epithelial cell line (Nthy-ori 3-1, hereafter Nthy) treated with concentrations of BPA, BPS, or BPF ranging from 10-4 M down to 10-10 M. Following a five-day incubation, there was a significant increase in cell viability/ATP production in even the least concentrated treatment conditions compared to DMSO control. We also demonstrated the effect of BPA, BPS, and BPF treatment in a 3D cell culture model. 3D Nthy spheroids treated with 10-7 M BPA, BPS, BPF, or DMSO showed an up to three-fold increase in spheroid size with bisphenols compared to DMSO. A 3D CellTiter-Glo cell viability assay was used to validate these findings. Further, as these in vitro models do not fully recapitulate thyroid structure or function, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were orally gavaged with 10 mg/kg of bisphenol daily for three weeks. Histologic analysis of the thyroids post-treatment showed a decrease in follicle area with bisphenol treatment compared to DMSO, potentially indicating some impairment of thyroid function. Together, these results show that BPS and BPF are not biologically inert and that they demonstrate an effect on thyroid cell growth and architecture in a manner similar to that of BPA. These findings could provide evidence to support new legislative regulation on bisphenol usage, as no regulation currently exists for these compounds outside of BPA’s usage in products for infants.