Protective effects of prenatal administration of folic acid on retinoic acid-induced cellular damages of Meckel's cartilage in rats

Abstract

Craniofacial malformations are among the most common congenital deformities. Meckel's cartilage plays a major role in the development of the mandible and is highly susceptible to maternal teratogenic drug use. We therefore investigated possible protective effects of prenatal administration of folic acid on a retinoic-acid induced maxillofacial defect model. Sprague-Dawley pregnant female rats (n = 36) were used in this study. Retinoic acid was administered orally at the dose of 40, 60, or 80 mg/kg respectively on gestational day 8. Folic acid of 4.0 mg/kg was injected intraperitoneally on 7th, 8th and 9th days of pregnancy. Animals were sacrificed on the day 17th. Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused severe ultrastructural damages in Meckel's cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg. In addition, there was a marked decrease in the number of degenerated chondrocytes and an improvement in the structure of granular endoplasmic reticulum along with intact nuclei. We conclude that folic acid has protective effects on retinoic acid-induced intracellular damages in Meckel's cartilage. © 2005 Tohoku University Medical Press.