Low-dose Bisphenol A and its analogues Bisphenol F and S activate estrogen receptor ß and slightly modulate genes in human gingival keratinocytes.

Objectives: This study investigated the putative activation of estrogen receptor β (ERβ) and possible effects related on gene expression in oral mucosal cells in response to the endocrine disruptor Bisphenol A (BPA) and its analogues Bisphenol F (BPF) and Bisphenol S (BPS).
Methods: Human gingival keratinocytes (HGK) were exposed to BPA-, BPF-, and BPS-solutions in concentrations of 1.3 μM, 0.16 μM and 11.4 nM as well as 200 pM and 100 nM estradiol (E ₂ ) for 6 h, 24 h and 4 d. Indirect immunofluorescence (IIF) was performed to detect a possible ERβ activation. Additionally, transcription of keratinocyte-relevant biomarkers was analyzed by quantitative real-time PCR (qRT-PCR). A linear mixed model and pairwise comparisons were applied for statistical analyses.
Results: The tested concentrations of BPA, BPF, BPS and E ₂ revealed distinct activation of ERβ at all time periods, whereat 100 nM E ₂ induced the most pronounced activation. Despite the detected ERβ activation, the concentrations of BPA and its analogues induced only moderate modulation of the tested keratinocyte-relevant biomarker genes at all time periods. This also applied to 200 pM E ₂ , while in case of 100 nM E ₂ significant changes (p < 0.05) were detected for almost all analyzed genes.
Significance: Though BPA and its analogues induce activation of ERß irrespective from the chosen concentrations and incubation periods, they lack significant modulation of gene expression of keratinocyte-relevant biomarkers. Although limited to a selected number of genes, the sparse modulation of gene expression may give a hint that the substances do slightly affect transcription of gingival-keratinocyte-innate genes, since the concentrations applied to HGK were of physiological importance.
(Copyright © 2021 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.)