Valproic acid-induced placental and teratogenic effects in rats.

Studies on teratogenicity and pathology of the cenceptus were conducted in Sprague-Dawley rats treated with 600, 800, and 1,000 mg/kg valproic acid po on day 13 of pregnancy. Each of the three doses was maternotoxic and caused (1) resorptions and/or abortions, reduction in the number of live fetuses per litter and mean fetal weight, and defects of the tail, rib and phalanx; and (2) degenerative changes in the labyrinth (thrombosis, angiectasis in the maternal lacunar network, necrosis of cytotrophoblasts and suppressed proliferation of fetal capillaries), reduced diameter nearing obliteration of umbilical vessels, with or without karyorrhexis of embryonic tissues. The lesions in the placental labyrinth were specific but, in the embryonic tissues, they were generalized. It was postulated that the vascular lesions in the labyrinth and umbilicus may have influenced embryonic development by reducing maternoembryonic gaseous and nutritional exchange.