Cleft lip and palate in mice treated with 2,3,7,8-tetrachlorodibenzo-p- dioxin: A morphological in vivo study

Tomohiro Yamada, Katsuaki Mishima, Kumiko Fujiwara, Hideto Imura, Toshio Sugahara

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

It is well-known that TCDD (2,3,7,8, tetrachloridedibenzo-p-dioxin) induces cleft palates (CPs) in pregnant C57BL mice. However, it is unclear if TCDD is a possible teratogen for cleft lip. We examined maxillofacial malformations including cleft lip in three animal strains: A/J mice, C57BL/6J mice and ICR mice. The A/J mouse develops cleft lip and palate spontaneously at a 5-10% rate. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 10 μg/kg, 20 μg/kg, or 40 μg/kg to examine the dose-response, and on a single day from GD 8.5-14.5 to examine the timing effects of TCDD administration on lip and palate formation. Furthermore, the palatal shelf movements during GD 8.5-14.5 were observed with a stereoscopic microscope. All embryos had cleft palates when the TCDD was administered just before palatogenesis (GD11.5-GD12.5). With respect to the TCDD effects, there were large differences among the strains. In the A/J mice, the difference between a lethal dose and a dose that could induce a cleft palate was close. Cleft lips were not induced, even when the TCDD was given just before labiogenesis. Morphologically, both palatal shelves contacted perfectly along their lengths, but separated and formed cleft palates. In conclusion, TCDD is a strong inducer of cleft palates, and interferes with the fusion phase of the secondary palate, but has no effect on the lip.

Original languageEnglish
Pages (from-to)21-25
Number of pages5
JournalCongenital Anomalies
Volume46
Issue number1
DOIs
Publication statusPublished - Mar 1 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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