Use of Dental Defects Associated with Low-Dose di(2-Ethylhexyl)Phthalate as an Early Marker of Exposure to Environmental Toxicants

• Ai Thu Bui ^[3] ; Sophia Houari ^[4] ; Sophia Loiodice ^[4] ; Dominique Bazin ^[1] ; Jérémy Sadoine ^[5] ; Nicolas Roubier ^[6] ; Elsa Vennat ^[1] ; Thu Thuy Tran ^[7] ; Ariane Berdal ^[4] ; Jean-Marc Ricort ^[3] ; Sakina Mhaouty-Kodja ^[2] ; Sylvie Babajko ^[3]
  1. [1] University of Paris-Saclay

     University of Paris-Saclay

     Arrondissement de Palaiseau, Francia

     
  2. [2] Pierre and Marie Curie University

     Pierre and Marie Curie University

     París, Francia

     
  3. [3] Laboratory of Molecular Oral Pathophysiology, Centre de Recherche des Cordeliers, Institut national de la santé et de la recherche médicale Unité mixte de recherche 1138 (Inserm UMRS 1138), Université Paris Cité, Sorbonne Université, Paris, France
  4. [4] Laboratory of Molecular Oral Pathophysiology, Centre de Recherche des Cordeliers, Institut national de la santé et de la recherche médicale Unité mixte de recherche 1138 (Inserm UMRS 1138), Université Paris Cité, Sorbonne Université, Paris, France; Department of Oral Biology, Dental Faculty, Université Paris Cité, Paris, France
  5. [5] EA 2496 Laboratory of Orofacial Pathologies, Imaging and Biotherapies, Dental School, Université Paris Cité, Montrouge, France
  6. [6] Laboratory of Mechanics of Soils, Structures and Materials, Le Centre national de la recherche scientifique (CNRS), Centrale-Supélec, Université Paris-Saclay, Châtenay-Malabry, France
  7. [7] Faculty of Odonto-Stomatology, Ho Chi Minh University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

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• Localización: Environmental health perspectives, ISSN 0091-6765, Vol. 130, Nº. 6, 2022
• Idioma: inglés
• DOI: 10.1289/EHP10208
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• Resumen

  • Markers of exposure to environmental toxicants are urgently needed. Tooth enamel, with its unique properties, is able to record certain environmental conditions during its formation. Enamel formation and quality are dependent on hormonal regulation and environmental conditions, including exposure to endocrine disrupting chemicals (EDCs). Among EDCs, phthalates such as di-(2-ethylhexyl) phthalate (DEHP) raise concerns about their contribution to various pathologies, including those of mineralized tissues.

    The effects of exposure to low-doses of DEHP on the continually growing incisors were analyzed in mouse males and females.

    Adult male and female C57BL/6J mice were exposed daily to 0.5, 5, and 50μg/kg per day DEHP for 12 wk and their incisors clinically examined. Incisors of males were further analyzed by scanning electron microscopy (SEM), micro X-ray computed tomography (micro-computed tomography; μCT), and nanoindentation for the enamel, histology and real-time quantitative polymerase chain reaction (RT-qPCR) for the dental epithelium.

    Clinical macroscopic observations of incisors showed various dose-dependent dental lesions such as opacities, scratches, and enamel breakdown in 30.5% of males (10 of 34 total incisors across three independent experiments), and 15.6% of females (7 of 46 incisors) at the highest dose, among which 18.1% (6 of 34 total incisors across three independent experiments) and 8.9% (4 of 46 incisors), respectively, had broken incisors. SEM showed an altered enamel surface and ultrastructure in DEHP-exposed male mice. Further characterization of the enamel defects in males by μCT showed a lower mineral density than controls, and nanoindentation showed a lower enamel hardness during all stages of enamel mineralization, with more pronounced alterations in the external part of the enamel. A delay in enamel mineralization was shown by several approaches (μCT, histology, and RT-qPCR).

    We conclude that DEHP disrupted enamel development in mice by directly acting on dental cells with higher prevalence and severity in males than in females. The time window of DEHP effects on mouse tooth development led to typical alterations of structural, biochemical, and mechanical properties of enamel comparable to other EDCs, such as bisphenol A. The future characterization of dental defects in humans and animals due to environmental toxicants might be helpful in proposing them as early markers of exposure to such molecules. https://doi.org/10.1289/EHP10208