title: Indole-3-acetic acid induces microencephaly in rat fetuses.
abstract: Indole-3-acetic acid (IAA), known as natural auxin, induces cleft palate in rodents. However, there has been no report about the neurodevelopmental toxicity of IAA in rats. In the present study, we found microencephaly in the fetuses from the rats exposed to IAA. The purpose of this work was to examine the effects of IAA administration in pregnant rats on neuroepithelial cells in the embryos/fetuses. IAA was administered at 500 and 1,000 mg/kg on gestation days (days) 12, 13, and 14, and then embryos/fetuses were harvested on days 14.5, 15, 16, and 21. Cleft palate was induced at 1,000 mg/kg. The brain in treated groups exhibited reduction in the size and weight on day 21 in a dose-dependent manner. Histopathologically, apoptotic cells were observed mainly in the medial and dorsal layer of the neuroepithelium at 500 and 1,000 mg/kg on day 14.5. On day 15, they were observed in the medial and dorsal layer of the neuroepithelium, and preplate at 1,000 mg/kg. On day 16, they existed in the dorsal layer of the neuroepithelium and intermediate zone in the embryos from 1 dam at 1,000 mg/kg. On day 21, an increase in cell proliferative activity was observed in the neuroepithelium at 500 and 1,000 mg/kg. The reduction of the cortical plate, the enlargement of the neuroepithelium and a slight increase in neuron density in the intermediate zone were observed at 1,000 mg/kg. These findings indicated IAA might induce the neuronal apoptosis in the S phase and lead to microencephaly.
authors.affiliation: Biological Research Laboratories, Nissan Chemical Industries Ltd., 1470 Shiraoka, Minamisaitama Saitama 349-0294, Japan. furukawa@nissanchem.co.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Furukawa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Abe
authors.forename: Koji
authors.initials: K
authors.lastname: Usuda
authors.forename: Izumi
authors.initials: I
authors.lastname: Ogawa
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D007210:Indoleacetic Acids / Q000633:toxicity*; D008831:Microcephaly / Q000139:chemically induced* / Q000473:pathology*; D046569:Neuroepithelial Cells / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007210:Indoleacetic Acids; C030737:indoleacetic acid