Bisphenol A (BPA) is a widespread endocrine disruptor commonly used by plastic industries. More than 95% of the world population contains BPA (ng/ml) in biological fluids raising the question of its activity and potential adverse effects. Anecdotally, molar incisor hypomineralisation (MIH), an enamel pathology affecting 1518% of children, is increasing concurrently with ED related pathologies. Our previous data show that BPA impacts amelogenesis and generate similar enamel defects as those described for MIH. The aim of the present study is to identify BPA target genes in order to characterize the mechanism of action of low-dose BPA in enamel hypomineralisation. First, rats were exposed daily to 5 μg/kg per day BPA from the conception to the sacrifice. RNAs from microdissected dental epithelia were submitted to microarray analysis. Among the 19 239 tested RNAs, only 41 were modulated (more than 1.5-fold) by BPA. Interestingly, among these genes, amelogenin and enamelin coding for specific enamel matrix proteins were ones of the highly up-regulated. Four other genes involved in mineralization process, SLC5A8, SLC26A4, SLC44A4 and Carbonic Anhydrase VB also appeared as BPA target genes which expression modulation may explain enamel hypomineralisation. Second, in vitro analysis carried out on the rat ameloblastic HAT7 cells also showed transcriptional modulations of enamel gene expression by 10−9 M BPA. Further studies are currently underway to decipher transcriptional modulations in relation with steroid receptors (ERα and AR) involved in BPA effects during amelogenesis. In conclusion, we report that BPA impacts enamel synthesis through modulations of enamel key gene expression. Despite the small number of BPA target genes specifically expressed in ameloblasts, ubiquitous receptors such as ERα and AR are involved in BPA effect transmission. Thus, these data help to understand how irreversible enamel defects may be used as early marker of exposure to BPA some years before the diagnosis of related heavy pathologies.
16 - 20 May 2015
European Society of Endocrinology