Common hierarchies of susceptibility to the induction of neural tube defects in mouse embryos by valproic acid and its 4-propyl-4-pentenoic acid metabolite.
The teratogenic effects of valproic acid and its 4-propyl-4-pentenoic acid (4-en) metabolite were investigated in three inbred mouse strains that were known to possess differing sensitivity to heat-induced neural tube defects. In the heat-resistant DBA/2J strain, administration of either valproic acid or the metabolite during the critical period of neural tube development failed to produce any abnormal offspring. Similar treatment in the moderately heat-sensitive LM/Bc strain resulted in up to 19.8% exencephalic fetuses. The highly heat-sensitive SWV strain was also very susceptible to the induction of neural tube defects by either valproic acid or its 4-en metabolite. When administered on gestational day 8 plus 12 hours, the parent compound produced 35% exencephalic fetuses, while the metabolite had a response frequency of 32.4%. Thus, the hierarchy of susceptibility for the induction of neural tube defects in these inbred mouse strains was exactly the same whether the teratogen was a physical agent such as hyperthermia or a chemical compound such as valproic acid. If such diverse agents as these should interact to produce malformations, then it is possible that a wide variety of other agents might interact in a similar manner to produce neural tube defects.
Finnell
R H
RH
Department of Veterinary and Comparative Anatomy, College of Veterinary Medicine, Washington State University, Pullman 99164-6520.
Bennett
G D
GD
Karras
S B
SB
Mohl
V K
VK
D000818:Animals; D004198:Disease Susceptibility; D005229:Fatty Acids, Monounsaturated; D005260:Female; D005327:Fetal Resorption; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009436:Neural Tube Defects / Q000139:chemically induced / Q000235:genetics*; D011247:Pregnancy; D013045:Species Specificity; D013723:Teratogens; D014635:Valproic Acid
D005229:Fatty Acids, Monounsaturated; D013723:Teratogens; C058846:4-propyl-4-pentenoic acid; D014635:Valproic Acid