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Micro-dissection of Enamel Organ from Mandibular Incisor of Rats Exposed to Environmental Toxicants
Published on: March 29, 2018
Dioxin alters gene expression in mouse embryonic tooth explants
C Sahlberg1, E Peltonen, P-L Lukinmaa
1Department of Pediatric and Preventive Dentistry, Institute of Dentistry, Biomedicum Helsinki, FIN-00014 UNiversity of Helsinki, Helsinki, Finland. carin.sahlberg@helsinki.fi
Abstract:
Dioxins are ubiquitous environmental poisons that cause disturbances in developing organs, including the teeth. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at the cap stage leads to reduced tooth size and deformation of cuspal morphology. Our hypothesis was that TCDD affects the expression of genes specific for tooth development, which leads to these aberrations. Mouse embryonic E14 tooth germs were cultured for 24 hrs with/without 1 microM TCDD. Analysis of total RNA on Affymetrix arrays showed that TCDD altered the expression of 31 known genes by a fold factor of at least 2. Genes implied in tooth development expressed only slight changes. Genes active at the cap stage were selected for quantitative PCR analysis. Of these, the most highly up-regulated were Follistatin and Runx2, while TGFbeta1 and p21 were the most down-regulated genes. Incomplete tooth morphogenesis caused by TCDD may thus result from modified expression of developmentally regulated genes.
Insights
Exposure to dioxins like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during tooth development alters gene expression, leading to dental abnormalities. This study investigated TCDD
Area of Science:
- Environmental Toxicology
- Developmental Biology
- Dental Research
Background:
- Dioxins are widespread environmental pollutants with known adverse effects on developing organs.
- Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during critical tooth development stages can cause significant dental malformations.
Purpose of the Study:
- To investigate the molecular mechanisms by which TCDD disrupts tooth development.
- To identify specific genes involved in tooth morphogenesis that are affected by TCDD exposure.
Main Methods:
- Mouse embryonic tooth germs at the E14 stage were cultured in the presence or absence of 1 microM TCDD for 24 hours.
- Gene expression analysis was performed using Affymetrix arrays to identify differentially expressed genes.
- Quantitative PCR was employed to validate changes in key developmental genes.
Main Results:
- TCDD exposure altered the expression of 31 known genes by at least a two-fold change.
- While genes critical for tooth development showed minor changes, TCDD significantly impacted other genes.
- Key genes identified include up-regulation of Follistatin and Runx2, and down-regulation of TGFbeta1 and p21.
Conclusions:
- TCDD-induced tooth malformations, including reduced size and altered cusp morphology, are likely due to modified expression of developmentally regulated genes.
- The study highlights the impact of environmental toxins on intricate developmental pathways.
- Understanding these molecular changes provides insights into dioxin toxicity and potential therapeutic targets.
