Project description:Folate, and its synthetic form folic acid, function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-PROOF study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 µg folic acid and 500 µg vitamin B12 per day or a placebo during an intervention period of two years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n=44 folic acid/vitamin B12, n=43 placebo) using the Infinium HumanMethylation450 BeadChip. After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo, revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8 and NODAL genes, implicated in carcinogenesis and early embryonic development. Furthermore, serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173, 425 and 11 regions, respectively. Interestingly, for several members of the developmental HOX genes, DNA methylation was related to serum levels of folate. Long-term supplementation with folic acid and vitamin B12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.

Project description:The fertility of dairy cows is challenged during early lactation and better nutritional strategies need to be developed to address this issue. Combined supplementation of folic acid and vitamin B12 improves energy metabolism in the dairy cow during early lactation. Therefore, the present study was undertaken to explore the effects of this supplement on gene expression in granulosa cells from the dominant follicle during the postpartum period. Multiparous Holstein cows received weekly intramuscular injection of 320 mg folic acid and 10 mg vitamin B12 (treated group) beginning 24 (SD 4) d before calving until 56 d after calving, whereas the control group received saline. The urea plasma concentration was significantly decreased during the pre-calving period, and the concentration of both folate and vitamin B12 were increased in treated animals. Milk production and dry matter intake were not significantly different between the two groups. Plasma concentrations of folates and vitamin B12 were increased in vitamin-treated animals. Daily dry matter intake was not significantly different between the 2 groups before (13.5 kg SE 0.5) and after (23.6 kg SE 0.9) calving. Average energy-corrected milk tended to be greater in vitamin-treated cows, 39.7 (SE 1.4) and 38.1 (SE 1.3) kg/d for treated and control cows, respectively. After calving, average plasma concentration of BHBA tended to be lower in cows injected with the vitamin supplement, 0.47 (SE 0.04) vs. 0.55 (SE 0.03) for treated and control cows, respectively. The ovarian follicle ? 12 mm in diameter was collected by ovarian pick-up after estrus synchronization. Recovered follicular fluid volumes were greater in the vitamin-treated group. A microarray platform was used to investigate the impact of treatment on gene expression of granulosa cells. Lower expression of genes involved in the cell cycle and higher expression of genes associated with granulosa cell differentiation prior to ovulation were observed. Selected candidate genes were analyzed by reverse transcription quantitative polymerase chain reaction. Although the effects of intramuscular injections of folic acid and vitamin B12 on lactational performance and metabolic status of animals were limited, Ingenuity Pathway Analysis of gene expression in granulosa cells suggests a stimulation of cell differentiation in vitamin-treated cows, which may be the result of an increase in LH secretion. Two conditions experiment (Control and Treated). Granulosa cells from the 66h post second PGF2alpha injection. Biological replicates: 3 from each time point. Two technical replicates for each comparison (dye-swap).

Project description:The fertility of dairy cows is challenged during early lactation and better nutritional strategies need to be developed to address this issue. Combined supplementation of folic acid and vitamin B12 improves energy metabolism in the dairy cow during early lactation. Therefore, the present study was undertaken to explore the effects of this supplement on gene expression in granulosa cells from the dominant follicle during the postpartum period. Multiparous Holstein cows received weekly intramuscular injection of 320 mg folic acid and 10 mg vitamin B12 (treated group) beginning 24 (SD 4) d before calving until 56 d after calving, whereas the control group received saline. The urea plasma concentration was significantly decreased during the pre-calving period, and the concentration of both folate and vitamin B12 were increased in treated animals. Milk production and dry matter intake were not significantly different between the two groups. Plasma concentrations of folates and vitamin B12 were increased in vitamin-treated animals. Daily dry matter intake was not significantly different between the 2 groups before (13.5 kg SE 0.5) and after (23.6 kg SE 0.9) calving. Average energy-corrected milk tended to be greater in vitamin-treated cows, 39.7 (SE 1.4) and 38.1 (SE 1.3) kg/d for treated and control cows, respectively. After calving, average plasma concentration of BHBA tended to be lower in cows injected with the vitamin supplement, 0.47 (SE 0.04) vs. 0.55 (SE 0.03) for treated and control cows, respectively. The ovarian follicle ? 12 mm in diameter was collected by ovarian pick-up after estrus synchronization. Recovered follicular fluid volumes were greater in the vitamin-treated group. A microarray platform was used to investigate the impact of treatment on gene expression of granulosa cells. Lower expression of genes involved in the cell cycle and higher expression of genes associated with granulosa cell differentiation prior to ovulation were observed. Selected candidate genes were analyzed by reverse transcription quantitative polymerase chain reaction. Although the effects of intramuscular injections of folic acid and vitamin B12 on lactational performance and metabolic status of animals were limited, Ingenuity Pathway Analysis of gene expression in granulosa cells suggests a stimulation of cell differentiation in vitamin-treated cows, which may be the result of an increase in LH secretion.

Dataset Information

New Roles for Vitamin B12 Regulation

Publications

Elucidation of roles for vitamin B<sub>12</sub> in regulation of folate, ubiquinone, and methionine metabolism.

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