Valproic Acid-induced Skeletal Defects and Spina Bifida in Rat Fetuses

Among antiepileptic drugs valproic acid (VA) is a well known teratogenic agent. We previously reported that maternal administration of VA during critical periods of rat pregnancy can produce very rare CNS defect syringomyelia. The purpose of the present study was whether VA can affect other organs based on this finding we studied the teratogenic effects of it on rat developing skeletal system. Based on this experimental study 3 experimental groups of pregnant wistar rats were received single dose of 800 mg/kg VA on gestational days 9 -11 respectively. 3 Control groups were received the same volume of physiological serum at the same periods. On day 18th of gestation all pregnant rats were anesthetized and their fetuses were examined and histochemical study around their vertebral region were carried out. Our finding indicated different kinds of malformations in experimental groups which was consist of growth retardation embryonic absorbtion as well as skeletal system defect by special regard in vertebral column. These data revealed that the rate of spina bifida and vertebral abnormal flexions in experimental group 1 increased significantly in comparison experimental groups 2 and 3. These findings suggest that day 9th of rat pregnancy is critical period for vertebral column development and during this period of time VA or its metabolites may be interfere with developmental phenomena which can produce vertebral defects such as spina bifida.