Table 4:
Developmental Pb exposure and the epigenome in the context of cardiovascular health
| Exposure details | Window of exposure | Model | Epigenetic/molecular effect | Phenotype | Sex specificity | Reference |
|---|---|---|---|---|---|---|
| Pb concentrations in maternal urine at gestational week 8 and erythrocytes at gestational week 14 | Early gestation | Human | Significant inverse association between urinary Pb and cord blood DNA methylation at nine CpGs, including several in Glycoprotein 6 gene | Not investigated | Effects observed in both sexes | [129] |
| Pb levels in prenatal maternal red blood cells (average 27.9 weeks gestation) and cord blood | Mid-late gestation | Human | Significant negative association between maternal RBC Pb and cord blood DNA methylation at four CpGs in both sexes; several differentially methylated CpGs specific to males and females, including NOTCH1 and GNAS in females | Not investigated | Yes—More significantly differentially methylated CpGs in female vs. male infants | [132] |
| Maternal blood Pb at ∼12 weeks gestation | Early gestation | Human | Hypermethylation of the MEG3 imprinted regulatory domain in umbilical cord blood | Lower birth weight and rapid gains in adiposity at 2–3 years of age | Not reported | [133] |
| Serial blood Pb samples from birth to 78 months of age | Early childhood | Human | Mean blood Pb levels in childhood associated with a significant decrease in DNA methylation at IGF2/H19 and PEG3 loci and increased methylation at PLAGL1/HYMAI in peripheral blood in adulthood | Yes—Effects on PEG3 stronger in males; effects on IGF2/H19 stronger in females | Yes | [136] |
| 0, 100, or 500 ppb of Pb in petri dish water from <1 to 2 until 72 h post-fertilization (end of embryogenesis) | Embryogenesis | Zebrafish | Significant reduction in global DNA methylation in whole embryos at both doses; reduced transcript expression of dnmt3 and dnmt4 (human DNMT3B orthologs) | Not investigated | Not reported | [138] |
| 0, 2, 10, and 17 μg/l of Pb(NO3)2 in culture plate | 3–4 h to 7 days post-fertilization | Zebrafish | Down-regulation of Dnmt1 and Dnmt3b transcript expression in embryos | Increased malformations and decreased heart rate with Pb in combination with elevated temperature | Not reported | [139] |
| Pb acetate in drinking water | 2 weeks prior to mating, through gestation and lactation | Mouse | Sex-specific differential methylation of hundreds of CpGs and 1000 base pair regions in male and female offspring hearts in adulthood | Not investigated | Yes | [146] |