A preliminary study on the teratogenesis of dexamethasone and the preventive effect of vitamin B12 on murine embryonic palatal shelf fusion in vitro

Abstract

Excessive dexamethasone (Dex) administrated into pregnant mice during critical periods of palatal development can produce a high incidence of cleft palate. Its mechanisms remain unknown. Vitamin B 12 has been shown to antagonize the teratogenic effects of Dex, which, however, remains controversial. In this study, we investigated the effects of Dex and vitamin B 12 on murine embryonic palatal shelf fusion using organ culture of murine embryonic shelves. The explanted palatal shelves on embryonic day 14 (E14) were cultured for 24, 48, 72 or 96 h in different concentrations of Dex and/or vitamin B 12 . The palatal shelves were examined histologically for the morphological alterations on the medial edge epithelium (MEE) and fusion rates among different groups. It was found that the palatal shelves were not fused at 72 h or less of culture in Dex group, while they were completely fused in the control and vitamin B 12 -treated groups at 72 and 96 h, respectively. The MEE still existed and proliferated. In Dex+vitamin B 12 group the palatal shelves were fused at each time point in a similar rate to controls. These results may suggest that Dex causes teratogenesis of murine embryonic palatal shelves and vitamin B 12 prevents the teratogenic effect of Dex on palatogenesis on murine embryos in vitro.

Biological and epidemiological evidence of interaction of infant genotypes at Rs7205289 and maternal passive smoking in cleft palate

“…Mouse palatal shelf culture was carried out according to our previous study [Lu et al, 2008]. Palatal shelves of C57BL/6J mouse embryos were removed by using microsurgical shears and forceps under a dissecting microscope, and placed on 0.4‐µm porosity Millipore filters (Millipore Corporation, Carrigtwohill, Ireland) in 35‐mm tissue culture dishes.…”

Effect of vitamin B12 on cleft palate induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and dexamethasone in mice

“…Our previous studies also demonstrated that vitamin B 12 effectively restored DEX-induced failure of the palatal fusion in mice embryos (Lu et al, 2008). In our current study, we found that there was no significant difference in the palatal cleft incidence in Groups B and C (Table 1), and the size of palate between the two groups also had no distinguished difference.…”

“…Vitamin B 12 is one of the diverse vitamin B family members, which has extensively antagonistic effects on developmental toxicity and teratogenesis. Lu et al (2008) revealed that vitamin B 12 could effectively antagonize DEX-induced failure of the palatal fusion in mice embryos. However, an effect of vitamin B 12 on the combined toxicity of TCDD and DEX for palatal development has not been investigated.…”

Effects of vitamin B12 on murine embryonic dexamethasone-induced cleft palates using 1H-NMR-based metabonomic analysis

“…In recent years, Dex-induced cleft palates in mice have become a standard animal model of cleft palate etiology and an important tool for studying pathogenesis and treatment (Dudas et al 2004;Martinez-Alvarez et al 2004;Xu et al 2009). Some studies have shown that B 12 antagonizes the teratogenic effects of Dex on palate fusion in mouse embryos in vitro using the organ culture method (Hassell 1975;Lu et al 2008); another paper revealed the same effects of B 12 in a stereomicroscope study (He et al 2009). While it seems clear that B 12 antagonizes the effects of Dex, its mechanism remains unclear.…”