At high exposure levels arsenic has been associated with adverse pregnancy outcome. Defects in cardiovascular development are commonly associated with adverse pregnancy outcomes. This project examines the effect of in utero arsenic exposures in rodents on cardiovascular development in embryogenesis.
Investigators/Funding: Camenisch (RFG1), Runyan (RFG1), Billheimer (IHSFC-Biostats) SWEHSC Pilot Project, NIEHS/ES004940 (Superfund Component Project).
- This project examines the effect of in utero arsenic exposures in rodents on cardiovascular development in embryogenesis.
- Pregnant mice were exposed to environmentally relevant (10ppb-100ppb) concentrations of arsenite in drinking water.
- Embryos demonstrated dose-dependent cardiovascular development abnormalities including disrupted extravascular matrix (and matrix gene expression) around small arteries (50 ppb As), disrupted extravascular matrix patterning in carotid arteries (50 ppb As), changes in heart valve structure, and hypertension.
- Using heart explants cultures, As exposure dramatically attenuated epithelial to mesenchyman cell reduced vimentin expression in the cardiac cushion, attenuated Has2 and TGFb2 expression, decreased TGFb2 protein levels, increased rounding of cells, and altered embryonic heart myocardium. NIEHS ES06694, NIEHS/ES004940 (Superfund Component Project).