Effect of indole-3-acetic acid derivatives on neuroepithelium in rat embryos.

Indole-3-acetic acid (IAA), a natural auxin, induces microencephaly in rats exposed to IAA during gestation days (Days) 12-14, corresponding to the early stage of cerebral cortex development. The purpose of this study was to examine the effects of 5 IAA derivatives administration in pregnant rats on neuroepithelial cells in the embryos. N-Methylindole-3-acetic acid (1Me-IAA), 2-Methylindole-3-acetic acid (2Me-IAA), 2-Methyl-5-methoxyindole-3-acetic acid (2Me-5MeO-IAA), 5-Methoxyindole-3-acetic acid (5MeO-IAA), Indole butyric acid (IBA), and IAA were administered at 1,000 mg/kg except for 2Me-IAA at 500 mg/kg on Days 12, 13 and 14, and then embryos/fetuses were harvested on Day 14.5 or 21. The dams in the 1Me-IAA and 2Me-IAA groups exhibited rigidity and a decrease in locomotor activity. Although a decrease in the absolute brain weight was observed in the 1Me-IAA, 5MeO-IAA, IBA and IAA groups, a decrease in the relative brain weight was observed in only the IAA group. Histopathologically, apoptotic cells were observed mainly in the medial and dorsal layer of the neuroepithelium in the 5MeO-IAA and IAA groups on Day 14.5. The degree of induced neuroepithelial cell apoptosis was less in the 5MeO-IAA group than in the IAA group. However, it was confirmed that the histopathological changes induced by 5MeO-IAA were quite similar to the lesions induced by IAA and may have resulted from the same mechanisms.