Cardiogenic effects of trichloroethylene and trichloroacetic acid following exposure during heart specification of avian development

Toxicol Sci. 2006 Nov;94(1):153-62. doi: 10.1093/toxsci/kfl083. Epub 2006 Aug 17.

Abstract

Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCA) are common drinking water contaminants in the United States. Both chemicals have been implicated in causing congenital heart defects (CHD) in human epidemiological and animal model studies. However, the latter studies have primarily focused on assessment of cardiac morphology at late embryonic stages. Here, we tested whether treating avian embryos with TCE or TCA during an exposure window encompassing cardiac specification (Hamburger-Hamilton [HH] 3+) until the onset of chambering (HH 17) informs the etiology of CHD at later stages of development. Embryos were exposed to TCE or TCA via direct injection into the yolk, over a range of doses that included each compound's maximum contaminant level as established by the U.S. Environmental Protection Agency. A modified TUNEL (Terminal deoxynucleotide transferase mediated dUTP-biotin Nick-End Labeling) assay indicated that neither compound induced apoptotic cell death in ventricular myocytes or endocardiocytes at HH 18. However, mid-range dosages of TCE increased myocyte and endocardiocyte proliferation by this time, as determined by monitoring BrdU incorporation; in contrast, an intermediate dose of TCA inhibited proliferation in endocardiocytes. These cellular changes had no apparent functional consequences because all measured hemodynamic parameters were normal for TCE- and TCA-exposed embryos at HH 18, HH 21, and HH 23. In summary, TCE or TCA exposure during the cardiac specification window has only minimal effects on the developing avian heart. These results sharply contrast with our previously reported observations following administration of equivalent doses during a window of valvuloseptal morphogenesis. Taken together, these findings indicate that, as for other teratogens, sensitivity is dictated by the embryo's stage of development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Dose-Response Relationship, Drug
  • Endocardium / cytology
  • Endocardium / drug effects
  • Endocardium / embryology
  • Heart / drug effects*
  • Heart / embryology*
  • Heart Septal Defects / chemically induced
  • Heart Septal Defects / embryology
  • Heart Valve Diseases / chemically induced
  • Heart Valve Diseases / embryology
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects
  • Heart Ventricles / embryology
  • In Situ Nick-End Labeling
  • Myocytes, Cardiac / drug effects
  • Teratogens / toxicity
  • Time Factors
  • Trichloroacetic Acid / toxicity*
  • Trichloroethylene / toxicity*

Substances

  • Teratogens
  • Trichloroethylene
  • Trichloroacetic Acid