Lack of embryotoxicity of homocysteine thiolactone in mouse embryos in vitro.
Recent work from humans and chick embryos has suggested that homocysteine may play a role in producing neural tube defects (NTDs). In an effort to determine if homocysteine is able to produce NTDs in mammalian embryos, mouse embryos were explanted on GD 8 and cultured for 44 h. When either homocysteine or homocysteine thiolactone was added to the culture medium, treated embryos developed as well as controls and had closed neural tubes. Homocysteine thiolactone was also microinjected into the amniotic sac of mouse embryos. Again, development proceeded normally with no significant increase in the number of embryos with open neural tubes at the end of the culture period. HPLC analysis of embryonic thiols 24 h after microinjection revealed a significant increase in embryonic cystathionine levels. These data suggest that homocysteine does not produce NTDs in mouse embryos cultured in vitro and that early organogenesis-stage embryos are able to metabolize homocysteine.
Hansen
D K
DK
Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079-9502, USA. dhansen@nctr.fda.gov
Grafton
T F
TF
Melnyk
S
S
James
S J
SJ
D000014:Abnormalities, Drug-Induced; D000650:Amnion / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D006710:Homocysteine / Q000031:analogs & derivatives / Q000633:toxicity*; D066298:In Vitro Techniques; D051379:Mice; D008845:Microinjections; D011247:Pregnancy; D013438:Sulfhydryl Compounds / Q000378:metabolism; D018675:Toxicity Tests
D013438:Sulfhydryl Compounds; D006710:Homocysteine; C007957:homocysteine thiolactone