Oct4 plays a role in 2, 3, 7, 8 - tetrachlorobenzo-p-dioxin (TCDD) inducing cleft palate and inhibiting mesenchymal proliferation

• Published in: Toxicology (Amsterdam) 2020-05, Vol.438, p.152444, Article 152444
• Main Authors: Tao, Yuchang, Liu, Xiaozhuan, Cui, Lingling, Liu, Xinxin, Chen, Yao, He, Zhidong, Ji, Mengmeng, Gao, Zhan, Li, Ning, Wan, Zhongxiao, Yu, Zengli
• Format: Article
• Language: English
• Subjects: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); Cleft palate; Octamer-binding transcription factor 4; Proliferation
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2020.152444

•TCDD inhibited the proliferation of palatal mesenchyme in mice and promoted the apoptosis of it.•TCDD could activate the AhR signaling pathway when inducing cleft palate.•TCDD could inhibit Oct4 protein expression and induce cleft palate probably not by altering Oct4 promoter methylation levels. As a common birth defect, Cleft palate can be caused by the disturbance during the developmental process of the palatal shelves. The 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) is a well-known environmental teratogenic agent for cleft palate and Aryl hydrocarbon receptor (AhR) pathway can be activated by dioxins. Oct4 as a pluripotent stem cell transcription factor is also involved in the process of embryonic development. The AHR and retinoid receptors have cross-talk at CYP1A1 (cytochrome P450, family 1, subfamily A, polypeptide 1) promoter. There are also bidirectional talk between AhR and Oct4. In this study, we used C57/BL6 N mice and TCDD (64 μg/Kg body weight) to establish a model of fetal cleft palate to observe the effects of dioxin on fetal mesenchymal proliferation and apoptosis, and explore the role of Oct4 in inducing cleft palate. The results showed that dioxin inhibited mesenchymal proliferation and promoted apoptosis. In addition, dioxin inhibited Oct4 expression, and preliminary data suggest that hypermethylation of the Oct4 promoter may be a putative mechanism, suggesting that TCDD might induce cleft palate by inhibiting the proliferation of palatal mesenchymal cells mediated by Oct4.