Altered cardiac function and ventricular septal defect in avian embryos exposed to low-dose trichloroethylene.
Trichloroethylene (TCE) is the most frequently reported organic groundwater contaminant in the United States. It is controversial whether gestational TCE exposure causes congenital heart defects. The basis for TCE's proposed cardiac teratogenicity is not well understood. We previously showed that chick embryos exposed to 8 ppb TCE during cardiac morphogenesis have reduced cardiac output and increased mortality. To further investigate TCE's cardioteratogenic potential, we exposed in ovo chick embryos to TCE and evaluated the heart thereafter. Significant mortality was observed following TCE exposures of 8-400 ppb during a narrow developmental period (Hamburger-Hamilton [HH] stages 15-20, embryo day ED2.3-3.5) that is characterized by myocardial expansion, secondary heart looping, and endocardial cushion formation. Of the embryos that died, most did so between ED5.5 and ED6.5. Echocardiography of embryos at ED5.5 found that TCE-exposed hearts displayed significant functional and morphological heterogeneity affecting heart rate, left ventricular mass, and wall thickness. Individual embryos were identified with cardiac hypertrophy as well as with hypoplasia. Chick embryos exposed to 8 ppb TCE at HH17 that survived to hatch exhibited a high incidence (38%, p < 0.01, n = 16) of muscular ventricular septal defects (VSDs) as detected by echocardiography and confirmed by gross dissection; no VSDs were found in controls (n = 14). The TCE-induced VSDs may be secondary to functional impairments that alter cardiac hemodynamics and subsequent ventricular foramen closure, an interpretation consistent with recent demonstrations that TCE impairs calcium handling in cardiomyocytes. These data demonstrate that TCE is a cardiac teratogen for chick.
Rufer
Echoleah S
ES
Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Hacker
Timothy A
TA
Flentke
George R
GR
Drake
Victoria J
VJ
Brody
Matthew J
MJ
Lough
John
J
Smith
Susan M
SM
D000818:Animals; D002642:Chick Embryo; D004785:Environmental Pollutants / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006345:Heart Septal Defects, Ventricular / Q000139:chemically induced* / Q000196:embryology / Q000473:pathology; D018675:Toxicity Tests; D014241:Trichloroethylene / Q000633:toxicity*
D004785:Environmental Pollutants; D014241:Trichloroethylene