Maternal Vitamin D Deficiency Increases Intestinal Permeability and Programs Wnt/β‐Catenin Pathway in BALB/C Mice. Issue 1 (9th April 2020) - Yang, Kefeng
Abstract: Background: Recent studies suggest that vitamin D deficiency is associated with intestinal dysfunctions, but the underlying mechanism remains unclear. This study aimed to investigate whether maternal vitamin D deficiency increases intestinal permeability in offspring and its related mechanism. Methods: Timed‐pregnant mice were fed with either a standard chow diet (SC) or a vitamin D–deprived chow diet (VD‐) 6 weeks prior to breeding and kept on the same diet until the end of gestation. All offspring were fed an SC for 3 weeks after weaning and then observed for effects associated with maternal vitamin D deficiency. Results: Maternal vitamin D deficiency increased intestinal permeability in offspring, which corresponded with the decreased expression of the tight junction protein claudin‐1. Maternal vitamin D deficiency also repressed the messenger RNA expression of wingless/integrated family member 3a (Wnt3a) and the protein expression of nuclear β‐catenin. The decreased Wnt3a gene expression in male was concurrent with the changes in histone H4 acetylation at either promoter or coding regions. The activation of the Wnt/β‐catenin pathway protected against the impairment of intestinal permeability induced by maternal vitamin D deficiency. Conclusions: Maternal vitamin D deficiency increased intestinal permeability and decreased tight junction protein expression in offspring. The suppression of the Wnt/β‐catenin signaling pathway through histone modification might be involved in the underlying mechanism.