Effects of dietary zinc supply during pregnancy on global DNA methylation

Association of zinc level with DNA methylation and its consequences: A systematic review

“… Farahzadi, (2017) [ 15 ] Iran Six normal women, 45–58 years old) Methylation-specific qPCR Mesenchymal stem cells from adipose tissue Human telomerase reverse transcriptase (hTERT) Zinc deficient, zinc adequate/In-vitro Higher and lower levels of ZnSO 4 Among the 45 sites of CpG sites, 5 sites were changed to methylated, 9 sites were changed to unmethylated and 7 unmethylated sites and 10 methylated sites remained unchanged. Increased telomere length, the hTERT gene expression, and the telomerase activity Tian, (2013) [ 23 ] USA Female CD1 mice Immuno-fluorescence Oocytes Global DNA Fed zinc deficient and zinc control diet/in vivo Zinc deficiency Decrease in global DNA methylation in zinc deficient oocytes Increase Lap, Line-1, Sineb1 and Sineb2 transcription and decrease of Gdf9, Zp3 and Figla transcription, a significant reduction for the mature eggs to reach divided two cells Finke, (2020) [ 24 ] Germany 18, Male C57BL/6J mice High Performance Liquid Chromatography-Tandem Mass Spectrometry Jejunum, liver, cortex, and kidney Global DNA Fed zinc deficient and zinc control diet/in vivo Zinc deficiency No effect on the global DNA methylation and the hydroxymethylation Splenomegaly and genomic instability in the liver of mice Davison, (2010) [ 25 ] UK Pregnant mice and their pups Luminometric methylation assay (LUMA) assay using a pyrosequencer Pups liver Global DNA Zn-restricted, Zn-adequate or Zn-supplemented/in-vivo Zinc restriction, zinc supplementation Significantly higher methylation in zinc deficient and zinc supplementation Significant increase of DNMT1 and DNMT3a expression in higher zinc Jiang, (2020) [ 16 ] China 32 pregnant rats Quantitative real-time PCR. Methylation-specific PCR Hippocampus of offspring BDNF promoter Fed zinc deficient and zinc control diet/in vivo Zinc deficiency and zinc supplementation Reduction of BDNF methylation after zinc supplementation to offspring from zinc-deficient mother Supplementation of zinc at age 21 to 60, improved BDNF expre...…”

“…DNA methylation targets are included in a range of genomic locations. Eight studies examined gene-specific DNA methylation (SLC30A5, SLC30A6, PEG3, PLAGL1, MEG3, IFN-γ, IRF-4, hTERT, BDNF, MT2, IL-6) [ 12 – 19 ], and seven studies examined global DNA methylation using long interfering nuclear element-1 (LINE-1) and Arthrobacter luteus (Alu) genes as proxies for global DNA methylation [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. DNA methylation analysis utilized six different methods, bisulfite pyrosequencing (n = 5) [ 12 , 13 , 20 , 22 , 27 ] and methylation-specific qPCR (n = 4) [ [14] , [15] , [16] , 18 ], immune fluorescence (n = 2) [ 23 , 26 ], enzyme-linked immunosorbent assay (ELISA) (n = 1) [ 21 ], high-performance liquid chromatography-tandem mass spectrometry (HPLC TMS) (n = 1) [ 24 ], luminometric methylation assay (LUMA) (n = 1) [ 25 ], and bisulfite genomic sequencing (n = 1) [ 17 ].…”

“…However, depending on the severity of zinc deficiency there was a significant reduction in the ability of mature eggs to undergo cell division [ 23 ]. In mice, increased zinc levels and zinc deficiency in female mice had an impact on global DNA methylation in the livers of pups, which was associated with a considerable increase in the expression of DNMT1 and DNMT3 when compared to control mice [ 25 ]. However, zinc treatment showed to mitigate the effect of demethylation agents.…”

“…Zinc deficiency in rodents showed a significant increase in DNA methylation. Zinc deficiency significantly increased DNA methylation in the BDNF IX in the pup’s hippocampus [ 25 ]. Similarly, zinc supplementation to pups of zinc-deficient mothers, from the age of 21 days–60 days was found to reduce the DNA methylation of BDNF exon IX.…”

“…Zinc supplementation has been shown to regulate BDNF expression [ 45 ]. Hypermethylation of BNDF promoter in zinc-deficient pups was associated with a reduction in the expression of BDNF mRNA and DNMT3A mRNAs, whereas the DNMT1 mRNA was increased [ 25 ]. The protein level of BDNF, DNMT1 and GADD455b in neonates were reduced.…”