title: Trichloroethylene exposure during cardiac valvuloseptal morphogenesis alters cushion formation and cardiac hemodynamics in the avian embryo.
abstract: It is controversial whether trichloroethylene (TCE) is a cardiac teratogen. We exposed chick embryos to 0, 0.4, 8, or 400 ppb TCE/egg during the period of cardiac valvuloseptal morphogenesis (2-3.3 days' incubation) . Embryo survival, valvuloseptal cellularity, and cardiac hemodynamics were evaluated at times thereafter. TCE at 8 and 400 ppb/egg reduced embryo survival to day 6.25 incubation by 40-50%. At day 4.25, increased proliferation and hypercellularity were observed within the atrioventricular and outflow tract primordia after 8 and 400 ppb TCE. Doppler ultrasound revealed that the dorsal aortic and atrioventricular blood flows were reduced by 23% and 30%, respectively, after exposure to 8 ppb TCE. Equimolar trichloroacetic acid (TCA) was more potent than TCE with respect to increasing mortality and causing valvuloseptal hypercellularity. These results independently confirm that TCE disrupts cardiac development of the chick embryo and identifies valvuloseptal development as a period of sensitivity. The hypercellular valvuloseptal profile is consistent with valvuloseptal heart defects associated with TCE exposure. This is the first report that TCA is a cardioteratogen for the chick and the first report that TCE exposure depresses cardiac function. Valvuloseptal hypercellularity may narrow the cardiac orifices, which reduces blood flow through the heart, thereby compromising cardiac output and contributing to increased mortality. The altered valvuloseptal formation and reduced hemodynamics seen here are consistent with such an outcome. Notably, these effects were observed at a TCE exposure (8 ppb) that is only slightly higher than the U.S. Environmental Protection Agency maximum containment level for drinking water (5 ppb) .
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Drake
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Koprowski
authors.forename: John
authors.initials: J
authors.lastname: Lough
authors.forename: Norman
authors.initials: N
authors.lastname: Hu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Smith
mesh_terms: D000818:Animals; D017209:Apoptosis; D002642:Chick Embryo; D006346:Heart Septum / Q000187:drug effects* / Q000196:embryology / Q000503:physiopathology; D006439:Hemodynamics; D009024:Morphogenesis; D014241:Trichloroethylene / Q000494:pharmacology*
chemical_list: D014241:Trichloroethylene