Indole-3-acetic acid induces microencephaly in mouse fetuses.
To determine the effect of indole-3-acetic acid (IAA), known as natural auxin, on developing fetus, pregnant mice were injected with 500 or 1000 mg/kg on various gestation days (Days). With the repeated treatment during Days 7-15, the fetal brains exhibited a reduction in size and weight in a dose-dependent manner on Day 18. Histopathologically, hypoplasia of the cortical plate, piriform cortex, hippocampus and thalamus were observed. From the single treatment on 1 day during Days 9-14, the sensitive period of IAA-induced microencephaly was found to be during Days 10-13 and the most significant response in the fetuses was seen on Day 11 or 12. With the repeated treatment during Days 11-13, apoptotic cells mainly increased in the medial and dorsal layer of the neuroepithelium and prepalate with a reduction in cell density in the telencephalon, diencephalon, mesencephalon and metencephalon on Day 12.5. p53-positve cells were detected associated with apoptotic cells in neuroepithelium. Therefore, IAA administration to pregnant mice induces apoptosis mediated by p53 in the embryo's neuroepithelium, decreases formation of neurons and leads to microencephaly in the fetuses.
Furukawa
Satoshi
S
Biological Research Laboratories, Nissan Chemical Industries, Limited, 1470 Shiraoka, Minamisaitama, Saitama, Japan. furukawa@nissanchem.co.jp
Usuda
Koji
K
Abe
Masayoshi
M
Hayashi
Seigo
S
Ogawa
Izumi
I
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005865:Gestational Age; D007210:Indoleacetic Acids / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D008831:Microcephaly / Q000139:chemically induced / Q000473:pathology*; D046569:Neuroepithelial Cells / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D010937:Plant Growth Regulators / Q000633:toxicity*; D011247:Pregnancy; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000633:toxicity*
D007210:Indoleacetic Acids; D010937:Plant Growth Regulators; D013723:Teratogens; C030737:indoleacetic acid