Vitamin B12 Counteracts Dexamethasone-Induced Proliferation and Apoptosis During Key Periods of Palatogenesis in Mice

Abstract

B vitamins rescue cleft palate induced by glucocorticoids in rodents; however, the mechanism of this effect remains largely unknown. The objective of our study was to assess the effect of dexamethasone and Vitamin B12 on cell proliferation and apoptosis during palatogenesis. In our study, mesenchymal cell proliferation in mouse embryonic palates decreased when the subjects were administered dexamethasone at embryo day 13.5 (E 13.5). However, mesenchymal cell proliferation was increased after dexamethasone exposure at E 14.0 and E 14.5 in comparison with the control group. After Vitamin B12 treatment, proliferation of mesenchymal cells was restored. No apoptosis was detected until bilaterial palatal shelves adhered and formed a medial epithelium seam in the control group and Vitamin B12-treated group. However, the apoptotic cells were detected under the medial edge epithelium before the palate contacted after dexamethasone treatment. The results suggested that Vitamin B12 restored proliferation, which had been reduced by dexamethasone via a delayed cellular cycle and apoptosis. This study implies that Vitamin B12 may be used to prevent or alleviate cleft palate induced by dexamethasone during embryonic palatogenesis.

Maternal Vitamin B12 Status and Risk of Cleft Lip and Cleft Palate Birth Defects in Tamil Nadu State, India

“…Experimental animal and cell culture models of OFCs induced by cortisone, retinoic acid, and dexamethasone have shown that vitamin B 12 reduces the occurrence of chemically induced OFCs (Mann & Gautieri, 1973; He et al, 2010; Zhang et al, 2011). The relevance of these models for humans is uncertain as these studies used different methods, chemical exposures for OFC induction, and doses of vitamin B 12 .…”

“…Vitamin B 12 is an essential cofactor in folate-related 1-carbon metabolism, but its possible role in OFCs has received much less attention than folate. Experimental animal studies have provided some evidence of a causal role for poor maternal vitamin B 12 status in the etiology of OFCs (Mann & Gautieri 1973; He et al, 2010; Zhang et al, 2011), but studies of maternal vitamin B 12 status and OFCs in humans are few in number with varied methods and inconsistent results (van Rooij et al, 2003; Shaw et al, 2009; Vujkovic et al, 2010; Sutton et al, 2011; Wallenstein et al, 2013; Blanco et al, 2016). Further insight from human studies of the associations between maternal vitamin B 12 and folate nutrition and OFCs may lead to global public health efforts to prevent OFCs.…”

Increased MMAB level in mitochondria as a novel biomarker of hepatotoxicity induced by Efavirenz

“…Defective synthesis of adenosylcobalamin results in a disorder of methylmalonate and cobalamin metabolism [ 35 , 36 ]. Moreover, metabolism of vitamin B (12) is required for prevention of cell apoptosis [ 37 , 38 ]. Since in this study we showed that EFV treatment induces up-regulation of MMAB, it might also affect the metabolism of vitamin B (12).…”

Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Nonsyndromic Cleft Lip and/or Palate

“…Folate (folic acid) and cobalamin (vitamin B12) participate in the methylation cycle and act as cofactors in DNA and RNA biosynthesis, playing an essential role in cell differentiation and tissue growth as well as during embryogenesis (3). Studies using animal models have demonstrated a specific involvement of folate and cobalamin during palatogenesis (4).…”