[Homocysteine-induced neural tube defects in chick embryos and protection of folic acid].
To reveal whether homocysteine(HCY) will be able to induce neural tube defects (NTDs) and possible teratogenic mechanisms, and identify the interventional effects of folic acid and vitamin B12 on HCY-induced NTDs, 1274 chick embryos treated with L. D-HCY (0-16 mumol/embryo) were detected by the methods of teratogenic trial, scanning electron microscopy(SEM), Nile blue sulfate vital staining, TdT-mediated dUTP nick end labeling(TUNEL) methylgreen-pyronine special staining for showing nucleic acid, and interventional assay of folic acid and VB12 in different developmental stage. Results showed that HCY could induce teratogenesis in chick neurulation and organogenetic period, in dose-response relationship (P < 0.0001). The main forms of NTDs were exencephaly, cranioschisis and spina bifida. It has been first found that HCY could target excessive apoptosis of cells of embryonic nervous system, which consists with the sites of embryos developing NTDs. HCY could inhibit chick yolk sac vessel formation and blood circulation, and damage amniotic membrane. Under SEM it was observed that HCY resulted in abnormal ultrastructures, for example cavernous damages, atrophied microvilli and so on. After the injection of 5 micrograms/embryo folic acid, the teratogenicity of HCY (8 mumol/embryo) was significantly antagonized, the occurrence rate of NTDs was down from 43.5% to 0(P < 0.05). However, vitamin B12 (1 microgram/embryo) did not obviously attenuate the teratogenicity of HCY in day 6 chick embryos. These data prove that HCY per se causes dymorphogenesis of the neural tube. Apoptosis may play an important role in the etiopathology of NTDs. Folic acid can effectively prevent from the homocysteine-induced NTDS. Causes of homocysteine-induced NTDs may result from interaction or combination of different mechanisms.
Li
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National Center For Maternal and Infant Health, Beijing Medical University, Beijing 100083, China.
Li
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Chen
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Qi
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002642:Chick Embryo; D005492:Folic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000633:toxicity*; D009436:Neural Tube Defects / Q000139:chemically induced*; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D006710:Homocysteine; D005492:Folic Acid