Figure 1
Susceptibility windows of DNA-methylation due to environmental pollutants. The epigenome undergoes reprogramming at two relevant stages, the gametogenesis and the early embryo preimplantation representing vulnerable stages to enviornemental exposures. During gametogenesis and fertilization, a general demethylation followed by a re-methylation process occur, with the exception of imprinted genes. DNA-methylation patterns are reestablished by DNA methyl-transferases DNMT3a and DNMT3b [1]. 5 mC, 5-methylcytosine. BPA, bisphenol A. Cd, cadmium. As arsenic. Pb, lead. Hg, mercury.
Table 1
Methylation changes associated with smoking, POP, phthalates, and BPA exposure during pregnancy and childhood.
| Xenobiotic | Population | Sample | Exposure association | Reference | |
|---|---|---|---|---|---|
| Change | Sequence | ||||
| Prenatal exposure to tobacco smoke | Children from USA (n = 348) | Buccal cells | + | LINE1a, AXL, PTPRO | [21] |
| – | AluYb8 | ||||
| Women from USA (n = 90) | Peripheral blood granulocytes | – | SAT2 | [22] | |
| Mother-offspring pairs from UK (n = 800) | Cord and blood cells | + | GFI1b, ATP9 Ab, AHRR, CYP1 A1, CNTNAP2 | [23] | |
| – | KLF13b, MYO1G | ||||
| Pregnant women from USA (n = 34) | Placenta | – | CYP1 A1 | [28] | |
| PBDE47 | Mother-newborn pairs (n = 46) | Maternal and cord blood cells | – | TNFα | [77] |
| o,p’-DDTs | – | Aluc | |||
| o,p’-DDT, p,p’-DDT p,p’-DDE and PBDEs | Children at birth and/or age 9 (n = 358) | Blood cells | – | LINE1d | [83] |
| + | LINE1e | ||||
| Phthalates | Children from Taiwan (n = 256) | Blood cells | + | TNF-α | [86] |
| Children from USA (n = 235) | Cord blood and blood cells | +/– | LINE1, Alu | [87] | |
| Children from USA (n = 336) | Cord blood | + | IRAK4, ESM1, BRCA1, LASP1, IFT140 | [88] | |
| Mother-newborn pairs from China (n = 119) | Placenta | – | LINE1 | [89] | |
| Mother-newborn pairs from China (n = 220) | – | IGF2 | [90] | ||
| Mother-newborn pairs from USA (n = 179) | – | IGF2 | [91] | ||
| Bisphenol A | Preadolescent girls from Egypt (n = 60) | Buccal cells | – | X chromosome | [92] |
| Mother-newborn pairs from USA (n = 81) | Cord blood | + | BDNF | [93] | |
| Fetuses from USA (n = 12) | Placenta | +/– | LINE1 | [94] | |
[i] + Increased methylation. – Decreased methylation. aOnly in GSTM1 (Glutathione-S-transferase type M1)-present children. bMethylation changes were reverted over time. cAt birth. dLow level of exposure to DDTs plus PBDEs, at birth. eHigh level of exposure to DDTs plus PBDEs at birth. LINE1 (Long interspersed nuclear element 1). AluYb8 (Alu element members of the Yb8 family). AXL (AXL receptor tyrosine kinase). PTPRO (Protein tyrosine phosphatase, receptor type O). SAT2 (Spermidine/spermine N1-acetyltransferase family member 2). GFI1 (Growth factor independent 1 transcriptional repressor). ATP9 A (ATPase phospholipid transporting 9 A (putative)). AHRR (Aryl-hydrocarbon receptor repressor). CYP1 A1 (Cytochrome P450 family 1 subfamily A member 1). CNTNAP2 (Contactin Associated Protein-Like 2. KLF13 (Kruppel like factor 13). MYO1G (Myosin 1G). TNFα (Tumor necrosis factor alpha). IRAK4 (interleukin-1 receptor-associated kinase 4); ESM1 (endothelial cell-specific molecule 1). BRCA1 (breast cancer 1). LASP1 (LIM and SH3 Protein 1). IFT140 (Intraflagellar Transport 140). IGF2 (Insulin-like growth factor 2). BDNF (Brain-derived neurotrophic factor). PBDE (Polybrominated diphenyl ethers). DDT (Dichlorodiphenyltrichloroethane). DDE (Dichlorodiphenyldichloroethylene).
Table 2
Effects of air pollutants on DNA-methylation in newborns and children.
| Xenobiotic | Population | Sample | Exposure association | Reference | |
|---|---|---|---|---|---|
| Change | Sequence | ||||
| PM2.5 | Mother-newborn pairs from Belgium (n = 240) | Placenta | + | Global methylation | [37] |
| PM10 | Fetal growth restriction newborns (n = 80) and normal newborns from China (n = 101) | Placenta | + – | LINE1 HSD11B2 | [38] |
| PM2.5 | Hispanic and non-Hispanic children from USA (n = 940) | Buccal cells | + | iNOS, NOS3 | [39, 40] |
| PAHsa | Dominican and African American pregnant women-newborn pairs from USA (n = 56) | Cord blood cells | + | ACSL3 | [41] |
| PAHsa DNA-PAH adducts | Dominican and African American pregnant women-newborn pairs from USA (n = 164) | Cord blood cells | – + | Global methylation Global methylation | [42] |
| PAHsa | Dominican and African American pregnant women-newborn pairs from USA (n = 53) | Cord blood cells | + | IFNγ | [43] |
| PAHsb | Atopic children from USA (n = 256) | Blood cells | + | FOXP3 | [45] |
| PAHsc (benzo[b]fluorantene) | Children from Mexico City (n = 150) | Blood cells | + | LINE1 | [46] |
| Pyrenec 8-OHdG | + | PARP1 | |||
[i] + Increased methylation. – Decreased methylation. ETS (Environmental tobacco exposure). LINE1 (Long interspersed nuclear element 1). HSD11B2 (11-beta-hydroxysteroid dehydrogenase type 2). iNOS (Inducible oxide nitric sinthetase). NOS3 (Nitric oxide synthase 3 expressed in endothelial cells). ACLS3 (Acyl-CoA synthetase long-chain family member 3). IL4 (Interleukin 4). IFNγ (Interferon gamma). IFT140 (Intraflagellar transport 140). FOXP3 (Forkhead box protein P3). PARP1 (Poly (ADP-ribose) polymerase 1). aPAH concentrations was obtained from personal monitoring. bPAH concentration was obtained from daily at the EPA Supersite. cPAH content in PM10.
Table 3
Effects of metal exposure during pregnancy or childhood on DNA-methylation.
| Xenobiotic | Population | Sample | Exposure association | Reference | |
|---|---|---|---|---|---|
| Change | Sequence | ||||
| Pb | Newborn-mother pairs from Mexico (n = 103) | Cord blood cells | – | Alu, LINE1 | [52] |
| Children (3 months to 5 years) and mothers from USA (n = 43) | Blood cells | + – | 75 CpG sites 38 CpG sites | [53] | |
| Children and mothers from USA (n = 35) | Cord blood cells | +/– | 564 CpG sites | [54] | |
| Cd | Newborns from Bangladesh (n = 127) | Cord blood cells | + | Global DNA-methylation (newborns: boys) | [59] |
| – | Global DNA-methylation (newborns: girls) | ||||
| + | HISTH4 L, PAX9, APBB3, GAP43 | ||||
| – | PTPRN2 | ||||
| Mother-newborn pairs from USA (n = 17) | Cord and maternal blood cells | + | Genes related to transcriptional regulation and apoptosis (PRR13) | [61] | |
| Hg | Newborns from USA (n = 138) | Cord blood cells | + | 85 CpG sitesa | [63] |
| Newborns from USA (n = 321) | – | PON1 | [65] | ||
| As | Newborns from Bangladesh (n = 101) | Cord blood cells | + | Global DNA-methylation | [69] |
| Newborns from USA (n = 134) | + | 75 CpG sitesa | [70] | ||
| Newborns from Bangladesh (n = 44) | + | cg00498691 | [71] | ||
| Newborns from Bangladesh (n = 127) | – | LRRC26v, HOXB9, BRSK2 | [72] | ||
| Newborns from Thailand (n = 71) | + | p53 | [73] | ||
| Newborns from Bangladesh (n = 113) | + | LINE1, p16 | [74] | ||
| Vb | Children from USA (n = 163) | Buccal cells | – | IL4, IFNγ | [76] |
| Children from Mexico (n = 150) | + | APEX, PARP1 | [46] | ||
[i] + Increased methylation. – Decreased methylation. aNot related to any gene. bV content in PM10. HISTH4 L (Histone H4 family member). PAX9 (Paired box 9). APBB3 (Amyloid beta precursor protein binding family B member 3). GAP43 (Growth associated protein 43). PTPRN2 (Protein tyrosine phosphatase, receptor type N2). PRR13 (Proline-Rich Protein 13). PON1 (Paraoxonase 1). LRRC26 (Leucine rich repeat containing 26). HOXB9 (Homeobox B9). BRSK2 (BR serine/threonine kinase 2). p53 (Tumor protein p53). LINE1 (Long interspersed nuclear elements 1). p16 (Tumor protein p16). IL4 (Interleukin 4). IFNγ (Interferon gamma). APEX (Apurinic/apirymidine endonuclease). PARP1 (Poly (ADP-ribose) polymerase 1).