Histological and Immunohistochemical Studies to Determine the Mechanism of Cleft Palate Induction after Palatal Fusion in Mice Exposed to TCDD.

Abstract

Rupture of the basement membrane in fused palate tissue can cause the palate to separate after fusion in mice, leading to the development of cleft palate. Here, we further elucidate the mechanism of palatal separation after palatal fusion in 8-10-week-old ICR female mice. On day 12 of gestation, 40 μg/kg of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), sufficient to cause cleft palate in 100% of mice, was dissolved in 0.4 mL of olive oil containing toluene and administered as a single dose via a gastric tube. Fetal palatine frontal sections were observed by H&E staining, and epithelial cell adhesion factors, apoptosis, and cell proliferation were observed from the anterior to posterior palate. TUNEL-positive cells and Ki67-positive cells were observed around the posterior palatal dissection area of the TCDD-treated group. Moreover, in fetal mice exposed to TCDD, some fetuses exhibited cleft palate dehiscence during fusion. The results suggest that palatal dehiscence may be caused by abnormal cell proliferation in epithelial tissues, decreased intercellular adhesion, and inhibition of mesenchymal cell proliferation. By elucidating the mechanism of cleavage after palatal fusion, this research can contribute to establishing methods for the prevention of cleft palate development.

• Authors: Chisato Sakuma, Hideto Imura, Tomohiro Yamada, Azumi Hirata, Yayoi Ikeda, Masaaki Ito, Nagato Natsume
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 4 (Feb 13 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35216185 (Publication Type: Journal Article)

Chemical References

• Polychlorinated Dibenzodioxins

Topics

• Animals
• Apoptosis (drug effects)
• Basement Membrane (drug effects, metabolism, pathology)
• Cell Proliferation (drug effects)
• Cleft Palate (chemically induced, metabolism, pathology)
• Epithelium (drug effects, metabolism, pathology)
• Female
• In Situ Nick-End Labeling (methods)
• Male
• Mice
• Mice, Inbred ICR
• Palate (drug effects, metabolism, pathology)
• Polychlorinated Dibenzodioxins (adverse effects)