Table 1.
Summary of animal studies examining changes in offspring epigenome in response to maternal nutritional alterations during gestation.
| NUTRIENT | MODEL | ALTERATION | GENE/CpG INFLUENCED | EFFECT ON OFFSPRING | STUDY SIZE (n) | REFERENCE |
|---|---|---|---|---|---|---|
| 1. Folic Acid, Vitamin B12, Methionine | Sheep: liver | Reduced levels of B12, folic acid, methionine compared to control | 57 CpG loci | 4% of the 1,400 CpG islands examined had altered methylation status. 88% of altered CpG sites were hypomethylated relative to controls | 37 | 31 |
| 2. Folic Acid, Vitamin B12, Choline, L-methionine, Zinc, and Betaine | Mouse: lung | High-methyl diet compared to a low-methyl diet | 82 CpG loci on Zdhhc5, Vldlr, Spock2, Cited4, Cnnm1, Mpp5, Dguok, A3galt2, Zfp503, Rcor3, Rnd3, Cdc42ep1, Runx3, Nfatc1, Jak2 genes | No alteration in global methylation between diets; however, 82 CpG loci were differentially methylated. The high-methyl diet significantly increased severity of allergic air disease in the mice. | 105 | 32 |
| 3. Folic Acid, Vitamin B12, L-Methionine, Choline, Betaine, Zinc | Mouse: liver/kidney | Medium and high levels of methyl donor supplementation | Long terminal repeat of agouti gene | Significant increase in DNA methylation of LTR and expression of Agouti gene with high-methyl diet. Subsequent alteration in offspring to a healthier phenotype. | 759 | 33, 34 |
| 4. Choline | Rat: liver | Choline supplemented, control and deficient diets | Global Methylation, IGF2 gene | Choline deficiency resulted in significant global and IGF2 hypermethylation in liver samples when compared to controls. | 35 | |
| 5. Protein, Folic Acid | Rat: liver | Low protein intake (9% of diet) and Folic Acid supplements | GR, PPAR genes | GR and PPARα CpG methylation was lower with protein restricted diet alone. Folic Acid supplements prevented this decrease. | 30 | 38 |
| 6. Protein, Folic Acid | Rat: liver | Low protein intake (9% of diet) and Folic Acid supplements | IGF2, H19 genes | Significant increase in DNA methylation in imprinting control region of IGF2 and H19 with low-protein diet only. Supplementation with folic acid prevented this hypermethylation. | 9 | 39 |
| 7. Fat | Mouse: adipose tissue | High-fat diet (62% fat, 20% carbohydrate, 18% protein) | Histones H3K9 (adiponectin), H4K20 (leptin) | The high-fat diet increased methylation of H4K20 in the promoter region of the leptin gene. The control mice had lower H3K9 methylation at 2, 12, and 24 weeks of age. | 48 | 40 |
| 8. Fat | Mouse: brain tissue | High-fat diet (45% fat) during pregnancy of grandmother | GHSR gene | Significantly decreased methylation status at GHSR promoter of second generation offspring. | 6 | 41 |
Abbreviations: CpG, site where a cytosine nucleotide occurs next to a guanine nucleotide common area for DNA methylation; Zdhhc5, zinc finger DHHC domain containing 5; Vldlr, very low-density lipoprotein receptor; Spock2, sparc/osteonectin; Cited 4, Cbp/p300 interacting transactivator; Cnnm1, cyclin M1; Mpp5, palmitoylated 5; Dguok, deoxyguanosine kinase; A3galt2, α-1,3-galactosyltransferase 2; Zfp503, zinc finger protein NOLZ1; Rcor3, REST corepressor 3; Rnd3, Rho GTPase; Cdc42ep1, CDC42 effector protein; Runx3, runt-related transcription factor 3; Nfact1, nuclear factor of activated T cells; Jak2, Janus kinase 2; GR, glucocorticoid receptor; PPAR, peroxisomal proliferator-activated receptor; IGF2, insulin-like growth factor II; H19, imprinted maternally expressed noncoding transcript; H3K9, histone H3 lysine 9; H4K20, histone H4 lysine 20; GHSR, growth hormone secretagogue receptor.