Homocysteine interference in neurulation: a chick embryo model.
BACKGROUND
Periconceptional folic acid supplementation reduces the occurrence and recurrence risk of neural tube defects (NTD). Mothers of children with NTD have elevated plasma homocysteine levels. Administering homocysteine to chick embryos is reported to cause 27% NTD. Therefore, elevated plasma homocysteine levels per se or a disturbed homocysteine metabolism may be teratogenic to the embryo and may interfere with neural tube closure. Our aim was to obtain a chick embryo model to explore the interference of homocysteine in neural tube closure.


METHODS
Homocysteine or saline was administered to chick embryos in ovo at 3 hr, 30 hr, and 60 hr of incubation and harvested at 74 hr. Homocysteine was then applied to chick embryos in vitro at a defined time window of four to six somites and followed for 6 hr.


RESULTS
Homocysteine administration to chick embryos in ovo resulted in several malformations but not in an increased number of NTDs. Homocysteine administration to chick embryos in vitro resulted in a transient, dose-dependent widening of the anterior neuropore and closure delay of the rhombencephalic neuropore. After 16 hr of incubation the neural tube was closed.


CONCLUSIONS
The in vitro chick embryo model appears a good model to explore the interference of a disturbed homocysteine metabolism in neurulation.
Afman
L A
LA
Department of Pediatrics, University Medical Center Nijmegen, The Netherlands. L.Afman@cukz.umcn.nl
Blom
H J
HJ
Van der Put
N M J
NM
Van Straaten
H W M
HW
D000015:Abnormalities, Multiple / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D002642:Chick Embryo; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology; D006710:Homocysteine / Q000633:toxicity*; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000473:pathology; D009924:Organ Culture Techniques; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D006710:Homocysteine