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首页> 外文期刊>Birth defects research, Part B. Developmental and reproductive toxicology >Effects of the histamine H1 antagonist chlorcyclizine on rat fetal palate development.
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Effects of the histamine H1 antagonist chlorcyclizine on rat fetal palate development.

机译：组胺H1拮抗剂氯环嗪对大鼠胎儿fe发育的影响。

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BACKGROUND: The effects of histamine H1 antagonist chlorcyclizine on rat palate development were characterized following in utero exposure. METHODS: To identify the optimum dose for inducing cleft palate, pregnant rats were administered 30, 60, or 90 mg/kg chlorcyclizine on Gestation Days 11 to 14. Fetal palate gene expression was also assessed after 90 mg/kg chlorcyclizine at 8, 15 and 30 hours post-dose on Gestation Day 14 using microarray and qRT-PCR. RESULTS: Rats in the 60- and 90-mg/kg groups exhibited adverse clinical signs and body weight loss. Rats in the 90-mg/kg group also demonstrated increases in late resorptions and decreases in fetal weight. Effects in the low-dose group were limited to decreases in body weight gain. Fetal assessment on Gestation Day 21 revealed that findings were limited to the 60- and 90-mg/kg groups, and included cleft palate (80% of litters for both groups), high arched palate, small nose, micrognathia, high domed head, digits shortened/absent and small limb. The fetal incidence of cleft palate was higher at 90 mg/kg, thus this dose was selected to assess palate gene expression. The altered genes associated with chlorcyclizine-induced cleft palate included Wnt5a, Bmp2, Bmp4, Fgf10, Fgfr2, Msx1, and Insig1 but the magnitude of the change was relatively small (1.5- to 2-fold). CONCLUSIONS: Expression of several genes involved in palate, limb and digit development was altered in the fetal palate following in utero exposure to chlorcyclizine. The subtle perturbation and interplay of these genes may have profound effects on the dynamics of fetal palate development.
机译：背景：在子宫内暴露后，表征了组胺H1拮抗剂氯环嗪对大鼠上颚发育的影响。方法：为了确定诱导c裂的最佳剂量，在妊娠第11至14天给妊娠大鼠施用30、60或90 mg / kg的氯环利嗪，并在8、15、90毫克/ kg的氯环嗪后评估胎儿pa的基因表达。在妊娠第14天的给药后30小时，使用微阵列和qRT-PCR。结果：60和90 mg / kg组的大鼠表现出不良的临床体征和体重减轻。 90 mg / kg组的大鼠还表现出晚期吸收增加和胎儿体重减少。低剂量组的作用仅限于体重增加的减少。在妊娠第21天进行的胎儿评估显示，研究结果仅限于60和90 mg / kg组，包括c裂（两组的产仔数均为80％），高弓形，小鼻子，小念头，高圆顶头，手指缩短/缺位，肢体小。胎儿pa裂的发生率较高，为90 mg / kg，因此选择该剂量来评估pa基因的表达。与氯环嗪诱导的pa裂相关的改变的基因包括Wnt5a，Bmp2，Bmp4，Fgf10，Fgfr2，Msx1和Insig1，但变化幅度相对较小（1.5至2倍）。结论：子宫内暴露于氯环嗪后，胎儿pa中涉及到in，四肢和手指发育的几个基因的表达发生了改变。这些基因的微妙扰动和相互作用可能对胎儿上颚发育的动力学产生深远的影响。

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