Vitamin D deficiency during pregnancy affects the function of Th1/Th2 cells and methylation of IFN-γ gene in offspring rats

The effects of maternal vitamin D status on offspring's Th1/Th2 cell function and the related mechanisms have not been reported. In this study, we established the rat model of vitamin D deficiency during pregnancy. 48 female Sprague-Dawley rats (8 weeks old) were randomly assigned to three groups (n = 16/group): control group (fed with standard AIN-93 G diet until parturition), vitamin D deficiency group (VDD group, fed with vitamin D deficient diet until parturition) and vitamin D supplementation group (VDS group, fed with vitamin D deficient diet prior to mating and with standard AIN-93 G diet during pregnancy). At 4 weeks of age, the ratio of T helper type 1/T helper type 2 (Th1/Th2) cells and the levels of Th1/Th2 cytokines (IFN-gamma, IL-4, IL-5, IL-6, IL-10 and IL-13) in offspring rats were determined by Flow Cytometry and Meso Scale Discovery, respectively. Furthermore, DNA methyltransferase (DNMT) activity as well as the methylation levels of IFN-gamma and IL-4 genes were measured. As a result, rats in the VDD group showed a significant decrease in Th1/Th2 ratio and IFN-gamma level and an increase in IL-4 level. Additionally, up-regulated DNMT activity and increased methylation rate of IFN-gamma gene was shown in VDD offspring rats. Supplementation with vitamin D during pregnancy reversed the above abnormalities. In conclusion, maternal vitamin D deficiency affected the function of Th1/Th2 cells and methylation of IFN-gamma gene in offspring rats. Meanwhile, maternal vitamin D deficiency had the potential to regulate DNMT activity, which may determine the status of methylation.