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Thoracic skeletal defects and cardiac malformations: a common epigenetic link?
Andrea D Weston1, Terence R S Ozolins, Nigel A Brown
1Developmental and Reproductive Toxicology Center of Emphasis, Drug Safety Research, and Development, Pfizer Global Research and Development, Groton, Connecticut 06340, USA.
Birth Defects Research. Part C, Embryo Today : Reviews
|February 23, 2007
Summary
Drug-induced congenital heart defects (CHDs) in rats also caused skeletal malformations, suggesting a shared developmental pathway. Epigenetic factors may link these defects and offer targets for developmental toxicants.
Area of Science:
- Developmental biology
- Toxicology
- Genetics
Background:
- Congenital heart defects (CHDs) are common birth defects and frequently observed in animal teratogenicity studies.
- Cardiac malformations often co-occur with thoracic skeletal defects, suggesting a mechanistic link between cardiogenesis and skeletal development.
Purpose of the Study:
- To explore the mechanisms of drug-induced heart defects using a rat model.
- To investigate the co-occurrence of cardiac and thoracic skeletal malformations.
- To examine the role of epigenetic factors in heart and axial skeleton development.
Main Methods:
- Treatment of pregnant rats with dimethadione to induce heart malformations.
- Review of teratogenicity studies and genetic evidence from mice.
- Focus on epigenetic factors, including chromatin architecture and histone modifications.
Main Results:
- Dimethadione treatment resulted in a high incidence of heart malformations accompanied by thoracic skeletal malformations.
- The co-occurrence of cardiac and skeletal defects appears to be a general phenomenon caused by various teratogens.
- Shared genes involved in heart and axial skeleton development highlight a mechanistic link.
Conclusions:
- Epigenetic factors play a crucial role in the development of both the heart and axial skeleton.
- Developmental toxicants may disrupt histone modifications, leading to co-occurring cardiac and skeletal malformations.
- Further research into epigenetic mechanisms is warranted to understand and prevent these birth defects.
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