Tetrachlorodibenzo-p-dioxin-induced cleft palate because of partial loss of cell polarity to interfere with apoptosis during early developmental stage.

Chenghao LI; Wei HE; Tian Meng; Shengjun LU; Bing Shi

Return

Tetrachlorodibenzo-p-dioxin-induced cleft palate because of partial loss of cell polarity to interfere with apoptosis during early developmental stage.

Author: Chenghao LI ¹ ; Wei HE ¹ ; Tian MENG ¹ ; Shengjun LU ¹ ; Bing SHI ²
Author Information

1. Department of Cleft Lip and Palate Surgery, West China School of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China.
2. Department of Cleft Lip and Palate Surgery, West China School of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China. Email: shibingcn@sina.com.
Publication Type:Journal Article
MeSH: Abnormalities, Drug-Induced; etiology; prevention & control; Animals; Apoptosis; Biomarkers; analysis; Cell Polarity; Cleft Palate; chemically induced; prevention & control; Disease Models, Animal; Female; Fetus; Folic Acid; therapeutic use; Mice; Mice, Inbred C57BL; Polychlorinated Dibenzodioxins; toxicity; Pregnancy; RNA, Messenger; analysis; Receptors, Aryl Hydrocarbon; analysis; genetics; Teratogens; toxicity; Transforming Growth Factor beta3; analysis; genetics
From: Chinese Journal of Stomatology 2014;49(12):719-723
CountryChina
Language:Chinese
Abstract:
OBJECTIVEIn this study, folic acid (FA) was tested for antiteratogenic effects on Tetrachlorodibenzo-p-dioxin (TCDD)-induced cleft palate in fetal mice.
METHODSIn the present study, pregnant mice were dosed with TCDD 24 µg/kg and with or without FA 5 mg/kg body weight on gestation day 10. Control group mice received sesame oil 50 ml/kg body weight on gestation day(GD)10. The mice were sacrificed on GD12.5, GD13.5, GD14.5, GD15.5 and GD16.5. From each pregnant mouse on GD16.5, embryos were obtained to examine under a dissecting microscope, and routine histology was performed for detection and classification of palatal clefts. The fetuses were prepared for histologic examination, scanning electron microscope and TdT-mediated X-dUTP nick and labeling (TUNEL). On GD12.5, GD13.5, GD14.5 and GD15.5. Meanwhile, real-time (RT)-PCR was employed to detect the mRNA expression levels about arylhydrocarbon receptor (AHR) and transforming growth factor (TGF)β3 in this animal model.
RESULTSTotal frequencies of clefts were 70.2% in TCDD group(group B) and 66.3% in TCDD+FA group(group C) in relation to control fetuses(group A). Filopodia disappeared completely at the medial edge epithelia surface on GD15.5 (group A), GD12.5 (group B) and GD14.5 (group C). the RT-PCR results showed that TGF -β3 expression was down-regulated on GD13.5 and GD14.5 compared to the control.
CONCLUSIONSIt is found that folic acid has no protects agaist 2.3.7.8-TCDD-indued cleft palate in the experiment. Meanwhile, TCDD repressed the TGF-β3 expression during the palatal development. Anormal apoptosis was induced by 2, 3, 7, 8-TCDD at the medial edge epithelia (MEE) during the early development stage.