Valproic Acid-Induced Time Dependent Craniofacial Defects in Wistar Rat Fetuse

Purpose: we previously reported that maternal valproic acid (VA) administration during rat pregnancy produced CNS defect ranely, syringomyelia. Furthermore, it seems that administration of valproic acid during critical period of pregnancy may affect on development of other embryonic skeletal portion such as craniofacial region. The goal of our study was to determine whether there is a relationship between maternal valproic acid exposure and craniofacial defects. Materials and Methods: In this study 3 groups pregnant wistar rats were received single dose of 800mg/kg VA on either 9th-11th days of gestation. The control groups were treated with the same volume of physiological serum at the same periods. For teratological studies, fetuses were examined on day 18th of gestation and histochemichal studies in craniofacial region were carried out. Results: However various malformations were observed among different experimental groups but the most important finding was craniofacial defects, such as cleft palate, hypoplasy of mandible microphtalmia among fetuses in group 2 (63%) in comparison to experimental groups 1 (18%) and 3 (16%). Histological study of craniofacial defects, showed some of abnormalities in components of face such as palatine processes and mandible. Conclusion: Among gestational days, these findings suggest that day 10th of rat pregnancy is critical period for face formation. Any teratogens such as VA may interfere with developmental phenomena which result in spectrum of craniofacial defects in mouse and probably in human.