Dental Defects Due To Exposure To DEHP, A Widespread Phthalate

Objectives: Contaminations by environmental pollutants such as endocrine disruptors (EDs) have been reported to contribute to increase the incidence and gravity of pathologies including dental diseases. Exposure to several EDs including bisphenol A (BPA), dioxin, PCBs is associated to enamel hypomineralization comparable to Molar Incisor Hypomineralization (MIH). The objectives of the present work is to search for and characterize dental defects generated in mice exposed to low-dose Di(2- ethylhexyl) phthalate (DEHP), a widespread phthalate used as a plasticizer.
Methods: Four weeks-old C57Bl6 mice were exposed to environmental-doses of DEHP from 0.5 to 50 µg/kg/day during eight weeks. Dental mineralized tissues, enamel and dentine, were analyzed by SEM, EDX, micro-CT and nanoindentation. Soft tissues, micro-dissected dental epithelium and mesenchyme, were analyzed for gene expression by RT-qPCR.
Results: 28% and 15% of mice exposed to DEHP presented enamel breakdowns and broken teeth, respectively, suggesting a weak dental structure. Enamel presented an altered surface whereas dentine didn’t show any evident defect. However, dentine presented reduced calcium content and hardness characteristics more importantly than enamel. RT-qPCR analysis showed that levels of Amelogenin, Enamelin, MMP20, SLC24A4, SLC26A4 were significantly up-regulated. In contrast, mesenchymal tissues showed a slight decrease in BSP, DMP1 and an important reduction of OPN. These data suggest that DEHP altered both amelogenesis and dentinogenesis explaining the weak dental quality that may lead to broken incisors. In vitro analysis is currently carried out to identify underlying molecular mechanisms.
Conclusions: In conclusion, our data showed that DEHP can disrupt enamel and dentine mineralization processes. Dental defects generated by exposure to DEHP are different than those generated by BPA suggesting different mechanisms of action and targeted genes. Characterization of dental defects may help to reconstitute the history of exposure to pollutants and use them as early marker of exposure to these molecules.