Endocrine Abstracts

MIH (Molar Incisor Hypomineralyzation) is a recently described enamel pathology that affects now 15 to 18% of children worldwide. Its prevalence increased similarly to other pathologies associated to exposure to Endocrine Disrupting Chemicals (EDCs). In addition, MIH affects selectively permanent first molars and incisors, the first developing teeth during the perinatal period also the time window with the highest susceptibility to EDCs. Our previous published data showed the bisphenol A (BPA) as a causal factor of MIH. In the present study, we compare the effects of BPA and Di(2-ethylhexyl) phthalate (DEHP) in male mice as both EDCs were widely used by plastic industry and found in many good consumers. Eight weeks-old C57bl6 mice were exposed to increasing dose of DEHP from 0.5 to 50 μg/kg/day during 4 weeks. Clinical observation of continually growing incisors showed 11% of teeth with enamel breakdown and 11% of completely broken teeth. MicroCT analysis revealed increased enamel volume contrary to BPA that decreased enamel volume and mineralization. Ameloblasts forming the dental epithelium are cells in charge of enamel synthesis. Their precise function changes during amelogenesis according to their stage of differentiation. They first secrete enamel matrix proteins (mainly amelogenin and enamelin) determinant for enamel thickness and volume, and second they expression many ion transporters (SLC26A family) and proteases (MMP20 and KLK4) necessary for the terminal and complete mineralization of enamel. RT-PCR analysis of microdissected dental epithelium showed that SLC26A4/pendrin is a common target gene of DEHP and BPA but MMP20 is modulated by DEHP only whereas enamelin by BPA only. In vitro analysis are currently carried out to identify underlying molecular mechanisms. In conclusion our data showed that several EDCs can disrupt amelogenesis but their target genes and mechanisms of action appeared different generating different enamel defects. Characterization of enamel defects may help to reconstitute the history of exposure to pollutants during the perinatal period and use them as early marker of exposure to these molecules.