Cardiac outflow tract malformations in chick embryos exposed to homocysteine.
OBJECTIVE
Increased homocysteine concentrations have been associated with cardiac outflow tract defects. It has been hypothesized that cardiac neural crest cells were the target cells in these malformations. Cardiac neural crest cells migrate from the neural tube and contribute to the condensed mesenchyme of the aorticopulmonary septum and outflow tract cushions of the heart. The aim of this study is to investigate the effects of homocysteine on cardiac neural crest cells in relation to heart malformations.


METHODS
Homocysteine was injected either into the neural tube lumen (30 micromol/l), or into the circulatory system (30 or 300 micromol/l) of chick embryos. LacZ-retroviral labeling was used to study cardiac neural crest cell migratory pathways after exposure to homocysteine.


RESULTS
Cardiac neural crest cells contributed to the aorticopulmonary septum of both control and homocysteine-treated embryos. However, the outflow tract of homocysteine-neural tube injected embryos displayed 60% less apoptosis and 25% reduced myocardialization. A subarterial ventricular septal defect was observed in 83% of the embryos. None of these abnormalities were observed in homcysteine-circulatory system injected embryos.


CONCLUSIONS
This study demonstrates that homocysteine disturbs apoptosis and myocardialization of the outflow tract, probably by affecting the cardiac neural crest cells.
Department of Anatomy and Embryology, Leiden University Medical Center, PO Box 9602, 2300 RC Leiden, The Netherlands.
Marit J
MJ
Boot
Régine P M
RP
Steegers-Theunissen
Robert E
RE
Poelmann
Liesbeth
L
van Iperen
Adriana C
AC
Gittenberger-de Groot
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000196:embryology / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D009432:Neural Crest / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D006710:Homocysteine