Teratogenic Effects of Valproate in the CD-1 Mouse Fetus

• Published in: Archives of neurology (Chicago) Vol. 42; no. 10; pp. 980 - 983
• Main Authors: Paulson, Ruth B, Sucheston, Martha E, Hayes, Thomas G, Paulson, George W
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.10.1985
• Subjects: Abnormalities, Drug-Induced - etiology; Abnormalities, Drug-Induced - pathology; Animals; Biological and medical sciences; Brain - abnormalities; Drug toxicity and drugs side effects treatment; Female; Fetal Diseases - chemically induced; Fetal Diseases - pathology; Medical sciences; Mice; Mice, Inbred Strains; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Pregnancy; Skull - abnormalities; Valproic Acid - adverse effects; Vertebrata; Mammalia; Mouse; Malformation; Toxicity; Animal; Rodentia; Anticonvulsant; Teratogen
• ISSN: 0003-9942; 1538-3687
• DOI: 10.1001/archneur.1985.04060090062015

• Valproate sodium has been implicated in the production of spina bifida in humans; this article reports an animal model. Teratogenicity of valproate sodium was studied by oral administration of single doses of 225, 340, and 560 mg/kg to pregnant CD-1 mice on days 7 through 12 of gestation. All fetuses were examined on day 17. Treated fetuses demonstrated external malformations and a decrease in weight. The incidence of malformations was greater at the higher dosage levels of 340 mg/kg and 560 mg/kg, with a predominance of exencephaly, open eyelids, and gross skeletal defects. There was a significant increase in the resorption rate of the fetuses in the treated groups. There was also a significant increase in the malformations observed per litter and per live fetus population when compared with controls.