Teratogenic Effects of Sodium Valproate in the Jcl: ICR Mouse Fetus

Sodium valproate was administered to Jc1:ICR mice in order to evaluate its teratogenicity. A single dose of 600 mg/kg of sodium valproate was injected intrapentoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized, and live fetuses were inspected for the presence of external and internal abnormalities. Exencephaly and urogenital abnormalities showed the highest frequency in the group treated on day 8, being recognized in about 60% and 10% of live fetuses, respectively. Cardiovascular abnormalities were found in the highest frequency in the group treated on day 7 (in about 30% of live fetuses). Incidence of tail abnormality was found to increase with delay in day of drug administration. Other abnormalities observed were cleft palate and digital malformation. Our study showed that a constellation of major abnormalities similar to the congenital valproate syndrome suspected in humans could be produced in the Jc1:ICR mouse fetus.