Cleft lip and palate in mice treated with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin: a morphological in vivo study
Cleft lip and palate in mice treated with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin: a morphological in vivo study
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DOI：
10.1111/j.1741-4520.2006.00097.x
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发表时间：
2006-03
影响因子：
1.3
通讯作者：
Tomohiro Yamada;K. Mishima;K. Fujiwara;H. Imura;T. Sugahara
中科院分区：
文献类型：
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作者：
Tomohiro Yamada;K. Mishima;K. Fujiwara;H. Imura;T. Sugahara
摘要众所周知，TCDD（2,3,7,8，四氯二苯并对二恶英）可诱导妊娠C57BL小鼠腭裂（CPs）。然而，目前尚不清楚TCDD是否可能是唇裂的致畸物。我们对A/J小鼠、C57BL/6J小鼠和ICR小鼠三种动物品系进行了包括唇裂在内的颌面部畸形的检测。A/J小鼠自发性唇腭裂发生率为5-10%。在妊娠第12.5天（GD）以10µg/kg、20µg/kg或40µg/kg的胃管给药橄榄油中TCDD以观察剂量反应，并在妊娠第8.5-14.5天的单天内观察TCDD给药对唇腭裂形成的定时效应。此外，用立体显微镜观察了GD 8.5 ~ 14.5期间腭架的运动情况。在腭裂发生前给予TCDD (GD11.5‐GD12.5)，所有胚胎均出现腭裂。在TCDD效应方面，菌株之间存在较大差异。在A/J小鼠中，致死剂量和诱发腭裂的剂量之间的差异非常接近。即使在唇裂发生前给予TCDD，也不会诱发唇裂。在形态学上，两个腭架沿其长度完全接触，但分开并形成裂腭。综上所述，TCDD是腭裂的强诱导剂，并干扰第二腭的融合期，但对唇部没有影响。
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.