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Phenytoin (dilantin)-induced cleft lip and palate in A/J mice: a scanning and transmission electron microscopic study
Insights
Phenytoin exposure during pregnancy disrupts embryonic facial development, causing cleft lip and palate (CLP) by altering mesenchymal cell structure in the lateral nasal process. This study details the cellular changes leading to CLP in mice.
Area of Science:
- Developmental Biology
- Teratology
- Craniofacial Development
Background:
- Cleft lip and palate (CLP) is a common birth defect.
- Maternal exposure to certain drugs during pregnancy can cause CLP.
- Phenytoin is an anticonvulsant drug with known teratogenic potential.
Purpose of the Study:
- To investigate the cellular mechanisms underlying phenytoin-induced cleft lip and palate (CLP) in A/J mice.
- To analyze the morphological changes in the lateral nasal process following phenytoin exposure.
Main Methods:
- Maternal intraperitoneal administration of phenytoin (75 mg/kg) on gestational day 10 in A/J mice.
- Scanning and transmission electron microscopy (EM) analysis of embryonic facial tissues.
- Comparison of mesenchymal cell morphology in phenytoin-treated versus control embryos.
Main Results:
- Phenytoin exposure led to a severe size reduction in the lateral nasal process.
- Mesenchymal cells in treated embryos showed undeveloped or absent cellular processes compared to controls.
- Observations suggest Simonart's bands form due to altered nasal and maxillary process fusion.
Conclusions:
- Phenytoin disrupts the development of mesenchymal cell structures crucial for normal facial fusion.
- These cellular alterations in the lateral nasal process are a key mechanism in phenytoin-induced CLP.
- Understanding these mechanisms can inform prevention and treatment strategies for CLP.
Abstract:
High incidences of cleft lip and palate (CLP) produced by maternal intraperitoneal administration of 75 mg/kg phenytoin on gestational day 10 to A/J mice are associated with a severe size reduction in the lateral nasal process. Scanning and transmission EM analyses of this region demonstrate a marked change in the morphology of the mesenchymal cells underlying the surface epithelium in treated versus control day 11 (7-tail somite) embryos: long, branching cellular processes, which form a dense meshwork that appears to interact with the epithelial basement lamina in control embryos are undeveloped or absent in phenytoin-treated embryos. The ultrastructural morphology of these cell processes is described and their possible importance in normal development is discussed. Scanning EM observations of incomplete clefts of the lip which frequently result from phenytoin treatment indicate that Simonart's bands form from fusion of the lateral and medial nasal processes in association with a lack of fusion of the maxillary process with the medial nasal process.