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Research Paper

Prenatal lead (Pb) exposure is associated with differential placental DNA methylation and hydroxymethylation in a human population

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Pages 2404-2420 | Received 25 Mar 2022, Accepted 12 Sep 2022, Published online: 23 Sep 2022

References

  • ATSDR. Agency for Toxic Substances and Disease Registry (ATSDR) - Toxicological profile for lead. 2020. Accessed 5 February 2022. https://www.atsdr.cdc.gov/ToxProfiles/tp13.pdf
  • Dignam T, Kaufmann RB, LeStourgeon L, et al. Control of lead sources in the United States, 1970-2017: public health progress and current challenges to eliminating lead exposure. J Public Health Manag Pract. 2019;25(Suppl 1 LEAD POISONING PREVENTION):S13–S22.
  • Nriagu JO. The rise and fall of leaded gasoline. Sci Total Environ. 1990;92:13–28.
  • Lanphear BP, Hornung R, Khoury J, et al. Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ Health Perspect. 2005;113(7):894–899.
  • Llanos MN, Ronco AM. Fetal growth restriction is related to placental levels of cadmium, lead and arsenic but not with antioxidant activities. Reprod Toxicol. 2009;27(1):88–92.
  • Jelliffe-Pawlowski LL, Miles SQ, Courtney JG, et al. Effect of magnitude and timing of maternal pregnancy blood lead (Pb) levels on birth outcomes. J Perinatol. 2006;26(3):154–162.
  • Bellinger DC. Very low lead exposures and children’s neurodevelopment. Curr Opin Pediatr. 2008;20(2):172–177.
  • Claus Henn B, Schnaas L, Ettinger AS, et al. Associations of early childhood manganese and lead coexposure with neurodevelopment. Environ Health Perspect. 2012;120(1):126–131.
  • Kordas K, Ardoino G, Coffman DL, et al. Patterns of exposure to multiple metals and associations with neurodevelopment of preschool children from Montevideo, Uruguay. J Environ Public Health. 2015;2015:1–9.
  • Tung PW, Burt A, Karagas M, et al. Association between placental toxic metal exposure and NICU Network Neurobehavioral Scales (NNNS) profiles in the Rhode Island Child Health Study (RICHS). Environ Res. 2022;204:111939.
  • Canfield RL, Henderson CR, Cory-Slechta DA, et al. Intellectual Impairment in children with blood lead concentrations below 10 µg per Deciliter. N Engl J Med. 2003;348(16):1517–1526.
  • Wasserman GA, Liu X, Popovac D, et al. The Yugoslavia Prospective Lead Study: contributions of prenatal and postnatal lead exposure to early intelligence. Neurotoxicol Teratol. 2000;22(6):811–818.
  • Weinhold B. Epigenetics: the Science of Change. Environ Health Perspect. 2006;114(3):A160–A167.
  • Relton CL, Hartwig FP, Davey Smith G. From stem cells to the law courts: DNA methylation, the forensic epigenome and the possibility of a biosocial archive. Int J Epidemiol. 2015;44(4):1083–1093.
  • Dou JF, Farooqui Z, Faulk CD, et al. Perinatal lead (Pb) exposure and cortical neuron-specific DNA methylation in male mice. Genes (Basel). 2019;10(4):274.
  • Wu S, Hivert MF, Cardenas A, et al. Exposure to low levels of lead in utero and umbilical cord blood DNA methylation in project viva: an epigenome-wide association study. Environ Health Perspect. 2017;125(8):087019.
  • Zeng Z, Huo X, Zhang Y, et al. Differential DNA methylation in newborns with maternal exposure to heavy metals from an e-waste recycling area. Environ Res. 2019;171:536–545.
  • Sanchez OF, Lee J, Yu King Hing N, et al. Lead (Pb) exposure reduces global DNA methylation level by non-competitive inhibition and alteration of dnmt expression†. Metallomics. 2017;9(2):149–160.
  • Pilsner JR, Hu H, Ettinger A, et al. Influence of prenatal lead exposure on genomic methylation of cord blood DNA. Environ Health Perspect. 2009;117(9):1466–1471.
  • Senut MC, Sen A, Cingolani P, et al. Lead exposure disrupts global DNA methylation in human embryonic stem cells and alters their neuronal differentiation. Toxicol Sci. 2014;139(1):142–161.
  • Dao T, Cheng RYS, Revelo MP, et al. Hydroxymethylation as a novel environmental biosensor. Curr Environ Health Rep. 2014;1(1):1–10.
  • Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300–1303.
  • Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–935.
  • Szulwach KE, Li X, Li Y, et al. Integrating 5-hydroxymethylcytosine into the epigenomic landscape of human embryonic stem cells. PLoS Genet. 2011;7(6):e1002154.
  • Bachman M, Uribe-Lewis S, Yang X, et al. 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat Chem. 2014;6(12):1049–1055.
  • Kinney SM, Chin HG, Vaisvila R, et al. Tissue-specific distribution and dynamic changes of 5-hydroxymethylcytosine in mammalian genomes*. J Biol Chem. 2011;286(28):24685–24693.
  • Li W, Liu M. Distribution of 5-hydroxymethylcytosine in different human tissues. J Nucleic Acids. 2011;2011:870726.
  • Santiago M, Antunes C, Guedes M, et al. TET enzymes and DNA hydroxymethylation in neural development and function — How critical are they? Genomics. 2014;104(5):334–340.
  • Cardenas A, Rifas-Shiman SL, Godderis L, et al. Prenatal Exposure to mercury: associations with global DNA methylation and hydroxymethylation in cord blood and in childhood. Environ Health Perspect. 2017;125(8):087022.
  • Rygiel CA, Goodrich JM, Solano -González M, et al. Prenatal lead (Pb) exposure and peripheral blood DNA methylation (5mC) and hydroxymethylation (5hmC) in Mexican adolescents from the ELEMENT birth cohort. Environ Health Perspect. 2021;129(6):067002.
  • Punshon T, Li Z, Marsit CJ, et al. Placental metal concentrations in relation to maternal and infant toenails in a US cohort. Environ Sci Technol. 2016;50(3):1587–1594.
  • Fortin JP, Triche TJ, Hansen KD. Preprocessing, normalization and integration of the illumina HumanMethylationEPIC array with minfi. Bioinformatics. 2017;33(4):558–560.
  • Aryee MJ, Jaffe AE, Corrada-Bravo H, et al. Minfi: a flexible and comprehensive bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics. 2014;30(10):1363–1369.
  • Triche TJ, Weisenberger DJ, Van Den Berg D, et al. Low-level processing of illumina infinium DNA methylation beadArrays. Nucleic Acids Res. 2013;41(7):e90.
  • Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118–127.
  • Leek JT, Johnson WE, Parker HS, et al. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28(6):882–883.
  • Green BB, Houseman EA, Johnson KC, et al. Hydroxymethylation is uniquely distributed within term placenta, and is associated with gene expression. FASEB J. 2016;30(8):2874–2884.
  • Fenton TR. A new growth chart for preterm babies: babson and Benda’s chart updated with recent data and a new format. BMC Pediatr. 2003;3(1):13.
  • Bakulski KM, Dou JF, Feinberg JI, et al. Prenatal multivitamin use and MTHFR genotype are associated with newborn cord blood DNA methylation. Int J Environ Res Public Health. 2020;17(24):9190.
  • Dou JF, Middleton LYM, Zhu Y, et al. Prenatal vitamin intake in first month of pregnancy and DNA methylation in cord blood and placenta in two prospective cohorts. Epigenetics Chromatin. 2022;15(1):28.
  • Pedersen BS, Schwartz DA, Yang IV, et al. Comb-p: software for combining, analyzing, grouping and correcting spatially correlated P-values. Bioinformatics. 2012;28(22):2986–2988.
  • Kamburov A, Wierling C, Lehrach H, et al. ConsensusPathDB—a database for integrating human functional interaction networks. Nucleic Acids Res. 2009;37(suppl_1):D623–D628.
  • Dantzer J, Ryan P, Yolton K, et al. A comparison of blood and toenails as biomarkers of children’s exposure to lead and their correlation with cognitive function. Sci Total Environ. 2020;700:134519.
  • Farzan SF, Howe CG, Chen Y, et al. Prenatal lead exposure and elevated blood pressure in children. Environ Int. 2018;121(Pt 2):1289–1296.
  • Esteban-Vasallo MD, Aragonés N, Pollan M, et al. Mercury, cadmium, and lead levels in human placenta: a systematic review. Environ Health Perspect. 2012;120(10):1369–1377.
  • Eid A, Bihaqi SW, Renehan WE, et al. Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer’s disease. Alzheimers Dement (Amst). 2016;2(1):123–131.
  • Schneider JS, Kidd S, Anderson DW. Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus. Toxicol Lett. 2013;217(1):75–81.
  • Bozack AK, Rifas-Shiman SL, Coull BA, et al. Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals. Clin Epigenet. 2021;13(1):208.
  • Globisch D, Münzel M, Müller M, et al. Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates. PLOS ONE. 2010;5(12):e15367.
  • Wen L, Tang F. Genomic distribution and possible functions of DNA hydroxymethylation in the brain. Genomics. 2014;104(5):341–346.
  • Pastor WA, Pape UJ, Huang Y, et al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature. 2011;473(7347):394–397.
  • Richa R, Sinha RP. Hydroxymethylation of DNA: an epigenetic marker. EXCLI J. 2014;13:592–610.
  • Iyengar GV, Rapp A. Human placenta as a “dual” biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 3: toxic trace elements in placenta and placenta as a biomarker for these elements. Sci Total Environ. 2001;280(1–3):221–238.
  • Rygiel CA, Dolinoy DC, Bakulski KM, et al. DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes. Environ Epigenet. 2021;7(1):dvab005.
  • Park J, Kim J, Kim E, et al. Prenatal lead exposure and cord blood DNA methylation in the Korean exposome study. Environ Res. 2021;195:110767.
  • Engström K, Rydbeck F, Kippler M, et al. Prenatal lead exposure is associated with decreased cord blood DNA methylation of the glycoprotein VI gene involved in platelet activation and thrombus formation. Environ Epigenet. 2015;1(1):dvv007.
  • Montrose L, Goodrich JM, Morishita M, et al. Neonatal lead (Pb) exposure and DNA methylation profiles in dried bloodspots. Int J Environ Res Public Health. 2020;17(18):6775.
  • Heiss JA, Téllez-Rojo MM, Estrada-Gutiérrez G, et al. Prenatal lead exposure and cord blood DNA methylation in PROGRESS: an epigenome-wide association study. Environ Epigenet. 2020;6(1):dvaa014.
  • Aung MT, Kelly M, Bakulski K, et al. Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI). Epigenetics. 2022;17(3):253–268.
  • Hong SB, Im MH, Kim JW, et al. Environmental lead exposure and attention deficit/hyperactivity disorder symptom domains in a community sample of South Korean school-age children. Environ Health Perspect. 2015;123(3):271–276.
  • Liu J, Liu X, Wang W, et al. Blood lead levels and children’s behavioral and emotional problems: a cohort study. JAMA Pediatr. 2014;168(8):737–745.
  • Ris MD, Dietrich KN, Succop PA, et al. Early exposure to lead and neuropsychological outcome in adolescence. J Int Neuropsychol Soc. 2004;10(2):261–270.
  • Mason LH, Harp JP, Han DY. Pb neurotoxicity: neuropsychological effects of lead toxicity. Biomed Res Int. 2014;2014:1–8.
  • Koukoura O, Sifakis S, Spandidos DA. DNA methylation in the human placenta and fetal growth (Review). Mol Med Rep. 2012;5(4):883–889.
  • Vlahos A, Mansell T, Saffery R, et al. Human placental methylome in the interplay of adverse placental health, environmental exposure, and pregnancy outcome. PLoS Genet. 2019;15(8):e1008236. Bartolomei MS, ed.
  • Bridges CC, Zalups RK. Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol. 2005;204(3):274–308.
  • Brini M, Calì T, Ottolini D, et al. Neuronal calcium signaling: function and dysfunction. Cell Mol Life Sci. 2014;71(15):2787–2814.
  • Kawamoto EM, Vivar C, Camandola S. Physiology and pathology of calcium signaling in the Brain. Front Pharmacol. 2012;3:61.
  • Lafond J, Hamel A, Takser L, et al. Low environmental contamination by lead in pregnant women: effect on calcium transfer in human placental syncytiotrophoblasts. J Toxicol Environ Health A. 2004;67(14):1069–1079.
  • Goyer RA. Transplacental transport of lead. Environ Health Perspect. 1990;89:101–105.
  • Kovacs CS, Kronenberg HM. Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation*. Endocr Rev. 1997;18(6):832–872.
  • Téllez-Rojo MM, Hernández-Avila M, Lamadrid-Figueroa H, et al. Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy. Am J Epidemiol. 2004;160(7):668–678.
  • Neal AP, Guilarte TR. Molecular neurobiology of lead (Pb2+): effects on synaptic function. Mol Neurobiol. 2010;42(3):151–160.
  • Cory-Slechta DA. Relationships between lead-induced learning impairments and changes in dopaminergic, cholinergic, and glutamatergic neurotransmitter system functions. Annu Rev Pharmacol Toxicol. 1995;35(1):391–415.
  • Alkondon M, Costa ACS, Radhakrishnan V, et al. Selective blockade of NMDA-activated channel currents may be implicated in learning deficits caused by lead. FEBS Lett. 1990;261(1):124–130.
  • Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem. 2001;1(6):529–539.
  • Görlach A, Bertram K, Hudecova S, et al. Calcium and ROS: a mutual interplay. Redox Biol. 2015;6:260–271.
  • Sasaki H, Nishizaki Y, Hui C, et al. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development. 1999;126(17):3915–3924.
  • Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013;14(7):416–429.
  • Ingham PW, Nakano Y, Seger C. Mechanisms and functions of Hedgehog signalling across the metazoa. Nat Rev Genet. 2011;12(6):393–406.
  • Ruiz I Altaba A. Catching a Gli-mpse of Hedgehog. Cell. 1997;90(2):193–196.
  • Fei DL, Li H, Kozul CD, et al. Activation of Hedgehog Signaling by the Environmental Toxicant Arsenic May Contribute to the Etiology of Arsenic-Induced Tumors. Cancer Res. 2010;70(5):1981–1988.
  • Kim J, Lee JJ, Kim J, et al. Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector. Pnas. 2010;107(30):13432–13437.
  • Winterbottom EF, Fei DL, Koestler DC, et al. GLI3 links environmental arsenic exposure and human fetal growth. EBioMedicine. 2015;2(6):536–543.
  • Morikawa M, Derynck R, Miyazono K. TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. 2016;8(5):a021873.
  • Massagué J, Blain SW, Lo RS. TGFβ signaling in growth control, cancer, and heritable disorders. Cell. 2000;103(2):295–309.
  • David CJ, Massagué J. Contextual determinants of TGFβ action in development, immunity and cancer. Nat Rev Mol Cell Biol. 2018;19(7):419–435.
  • Jones RL, Stoikos C, Findlay JK, et al. TGF-β superfamily expression and actions in the endometrium and placenta. Reproduction. 2006;132(2):217–232.
  • Gunatillake T, Yong HEJ, Dunk CE, et al. Homeobox gene TGIF-1 is increased in placental endothelial cells of human fetal growth restriction. Reproduction. 2016;152(5):457–465.
  • Caniggia I, Grisaru-Gravnosky S, Kuliszewsky M, et al. Inhibition of TGF-β3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest. 1999;103(12):1641–1650.
  • Goumans MJ, Liu Z, ten Dijke P. TGF-β signaling in vascular biology and dysfunction. Cell Res. 2009;19(1):116–127.
  • Zuscik MJ, Ma L, Buckley T, et al. Lead induces chondrogenesis and alters transforming growth factor-β and bone morphogenetic protein signaling in mesenchymal cell populations. Environ Health Perspect. 2007;115(9):1276–1282.
  • Beier EE, Jen ST, Dang D, et al. Heavy metal ion regulation of gene expression. J Biol Chem. 2015;290(29):18216–18226.
  • Liu RM, Desai LP. Reciprocal regulation of TGF-β and reactive oxygen species: a perverse cycle for fibrosis. Redox Biol. 2015;6:565–577.
  • Krstić J, Trivanović D, Mojsilović S, et al. Transforming growth factor-beta and oxidative stress interplay: implications in tumorigenesis and cancer progression. Oxid Med Cell Longev. 2015;2015:654594.
  • Chia N, Wang L, Lu X, et al. Hypothesis: environmental regulation of 5-hydroxymethylcytosine by oxidative stress. Epigenetics. 2011;6(7):853–856.
  • Tretter L, Adam-Vizi V. Inhibition of α-ketoglutarate dehydrogenase due to H2O2-induced oxidative stress in nerve terminals. Ann N Y Acad Sci. 1999;893(1):412–416.
  • Sen A, Cingolani P, Senut MC, et al. Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood. Epigenetics. 2015;10(7):607–621.

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