Bisphenol-A effect on Oral Cells: The Role of Estrogen Receptor-ß

Objectives: The aim of the present study was to evaluate the effect of low-dose bisphenol A (BPA) on gingival cells and to investigate the hypothesis of a mechanistic interrelationship between both, Calcium ion (Ca²⁺) influx and cell behavior and the estrogen receptor ß (ERß).
Methods: Indirect immunofluorescence (IIF) was conducted concerning the ERß activity for the periods of 1, 3, and 6 days after exposure to 39 nM BPA, 15 µM BPA, and 200 pM 17β-Estradiol (E₂). At these time periods a Ca²⁺ influx concentration measurement took place and a qPCR was performed for proliferation and differentiation biomarkers, to examine cell behavior. Fulvestrant-mediated ERß inhibition was used in order to evaluate the role of ERß on the effects caused by BPA exposure.
Results: E₂ and both concentrations of BPA induced ERβ activation. However, 39 nM BPA and 200 pM E2 reduced transcription of differentiation markers without changing MKI67 proliferation marker expression. 15 µM BPA reduced MKI67 transcription and increased significantly the differentiation gene expression and intracellular Ca²⁺ levels. Inhibition of ERß by Fulvestrant resulted in complete elimination of all previously observed E₂- and BPA modulatory effects. This finding supports the hypothesis that activated ERß plays a mechanistic role on BPA-mediated Ca²⁺ influx and keratinocyte differentiation.
Conclusions: The present findings suggest that both evaluated low-doses of BPA can cause a threshold-dependent transcription of proliferation and differentiation-related genes as well as Ca²⁺ influx. Is seems that activated ERß has an important role on the reaction of oral cells to BPA.