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

Autor: Bui AT; 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., Houari S; 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., Loiodice S; 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., Bazin D; Laboratory of Chemistry and Physics, Université Paris-Saclay, Orsay, France., Sadoine J; EA 2496 Laboratory of Orofacial Pathologies, Imaging and Biotherapies, Dental School, Université Paris Cité, Montrouge, France., Roubier N; Laboratory of Mechanics of Soils, Structures and Materials, Le Centre national de la recherche scientifique (CNRS), Centrale-Supélec, Université Paris-Saclay, Châtenay-Malabry, France., Vennat E; Institut Curie, Inserm U1196, Université Paris-Saclay, Orsay, France., Tran TT; Faculty of Odonto-Stomatology, Ho Chi Minh University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam., Berdal A; 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., Ricort JM; 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., Mhaouty-Kodja S; Neuroscience Paris Seine-Institut de Biologie Paris-Seine, CNRS, Inserm, Sorbonne Université, Paris, France., Babajko S; 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.
Jazyk: angličtina
Zdroj: Environmental health perspectives [Environ Health Perspect] 2022 Jun; Vol. 130 (6), pp. 67003. Date of Electronic Publication: 2022 Jun 22.
DOI: 10.1289/EHP10208
Abstrakt: Background: 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.
Objectives: The effects of exposure to low-doses of DEHP on the continually growing incisors were analyzed in mouse males and females.
Methods: Adult male and female C57BL/6J mice were exposed daily to 0.5, 5, and 50 μ g / 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; μ CT ), and nanoindentation for the enamel, histology and real-time quantitative polymerase chain reaction (RT-qPCR) for the dental epithelium.
Results: 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 μ CT 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 ( μ CT , histology, and RT-qPCR).
Discussion: 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.
Databáze: MEDLINE
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