Table 3. . Relationships between cadmium or lead exposure and epigenetic alterations .
| Author (year) | PMID | Study location | Sample size/characteristics | Exposure | Measured outcomes | Tissue source and assay type | Results | Ref. |
|---|---|---|---|---|---|---|---|---|
| Nye (2016) |
NA |
USA |
n = 321 mother–infant pairs |
Prenatal lead exposure |
Birth weight, changes in WHZ between birth to 1 year, 1–2 years and 2–3 years of age and DNA methylation |
Peripheral blood leukocytes (umbilical cord); pyrosequencing of H19, MEG3, PEG3 and PLAGL1 DMRs |
Prenatal lead exposure inversely associated with birth weight, positively associated with WHZ change by 2–3 years and hypermethylation at the MEG3 DMR regulatory region |
[74] |
| Sen (2015) |
26417717 |
USA |
n = 35 mother–infant pairs |
Prenatal lead exposure |
DNA methylation |
Dried blood spots: MNBS, CNBS, CCBS; 450K |
564 loci with altered DNA methylation in the CNBS of children whose mothers had high neonatal blood lead levels |
[75] |
| Vidal (2015) |
26173596 |
USA |
n = 319 mother–infant pairs |
Prenatal cadmium exposure |
Birth weight and DNA methylation |
Peripheral blood leukocytes (umbilical cord); pyrosequencing of IGF2/H19, MEG3, MEST, NNAT, PEG3, SGCE/PEG10 and PLAGL1 |
Higher maternal cadmium levels associated with lower birth weight and lower DNA methylation at the PEG3 DMR in female infants |
[12] |
| Li (2016) |
26115033 |
USA |
n = 64 females and n = 41 males ages 25–30 years (Blood lead concentration data available for these individuals at ages birth to 78 months) |
Early-life lead exposure |
DNA methylation of 22 imprinted genes |
Peripheral blood leukocytes; MassARRAY EpiTYPER |
Early-life lead exposure associated with sex-dependent DNA methylation differences in the imprinted gene DMRs of PEG3, IGF2/H19 and PLAGL1/HYMA1 |
[76] |
| Sen (2015) |
26077427 |
USA |
n = 25 males and n = 18 females from ages 3 months to 5 years |
Early-life lead exposure |
DNA methylation |
Dried blood spots; 450K |
Early-life lead exposure leads to 5-mC clustering into three sub-types: sex-specific and conserved. In the conserved subtype, increased DNA methylation around the transcription start site of LEP was identified. HIF3A is among the genes differentially methylated and associated with lead exposure in females |
[77] |
| Sen (2015) |
26046694 |
Mexico |
n = 24 female and n = 24 male infants and in vitro (hESCs) |
Prenatal lead exposure |
DNA methylation |
Umbilical cord blood; 450K and MeDIP-450K (modified 450K) |
Lead exposure associated 5-mC and 5-hmC clusters identified. These can be divided into sex-independent and sex-dependent categories with possible roles as early biomarkers of lead exposure |
[78] |
| Senut (2014) |
24519525 |
—— |
In vitro (hESCs) |
Lead exposure |
Neuronal differentiation and DNA methylation |
hESCs; 450K |
Lead exposure affects neuronal differentiation of hESCs altering number and morphology of generated neurons. Lead exposure also alters DNA methylation of genes involved in neurodevelopmental pathways |
[112] |
| Sanders (2014) |
24169490 |
USA |
n = 17 mother–infant pairs |
Prenatal cadmium exposure |
DNA methylation |
Maternal venous blood and umbilical cord blood; MIRA |
Cadmium exposure associated patterns of DNA methylation in maternal and newborn DNA |
[80] |
| Faulk (2013) |
24059796 |
—— |
In vivo (viable yellow agouti [Avy] mice) |
Early-life lead exposure |
Body weight and DNA methylation |
Tail DNA; coat color classification and pyrosequencing of imprinted Igf2 and Igf2r and metastable epiallele loci CabpIAP and Avy |
Dose and sex-specific effects were identified. Increase in wean body weight in males developmentally exposed to lead. Male specific effects at Avy locus. Altered coat color in Avy/a offspring |
[71] |
| Kippler (2013) |
23644563 |
Bangladesh |
n = 127 mother–infant pairs and n = 56 children age 4.5 years |
Prenatal cadmium exposure |
Birth weight and DNA methylation |
Umbilical cord blood and blood mononuclear cells from the 4.5-year-old children; 450K |
Maternal cadmium exposure associated with sex-specific changes to DNA methylation. CpG sites associated with cadmium exposure identified in both newborns and 4.5 year old children and cadmium-associated changes in methylation related to lower birth weight |
[81] |
| Schneider (2013) | 23246732 | —— | In vivo (rats) | Early-life lead exposure | Protein expression of Dnmts and methyl cytosine-binding proteins | Hippocampus; Western blot of DNA methyltransferases (Dnmt1, Dnmt3a) and methyl cytosine-binding protein (MeCP2, Mbd1) | Lead exposure affects Dnmt1 and Dnmt3a expression in the rat hippocampus. Expression of MeCP2 is affected by lead exposure in females | [82] |
CNBS: Child neonatal blood spots; CCBS: Child's current blood spot; Dnmts: DNA methyl-transferases; hESCs: Human embryonic stem cells; MIRA: Methylated CpG island recovery assay; MNBS: Maternal neonatal blood spots; NA: Not available; WHZ: Weight-for-height Z score.