{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T14:36:18Z","timestamp":1786804578282,"version":"build-2736575974"},"reference-count":117,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T00:00:00Z","timestamp":1642982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epigenetic modifications by toxic heavy metals are one of the intensively investigated fields of modern genomic research. Among a diverse group of heavy metals, lead (Pb) is an extensively distributed toxicant causing an immense number of abnormalities in the developing fetus via a wide variety of epigenetic changes. As a divalent cation, Pb can readily cross the placental membrane and the fetal blood brain barrier leading to far\u2010reaching alterations in DNA methylation patterns, histone protein modifications, and micro\u2010RNA expression. Over recent years, several human cohorts and animal model studies have documented hypermethylation and hypomethylation of developmental genes along with altered DNA methyl\u2010transferase expression by in utero Pb exposure in a dose\u2010, duration\u2010, and sex\u2010dependent manner. Modifications in the expression of specific histone acetyltransferase enzymes along with histone acetylation and methylation levels have been reported in rodent and murine models. Apart from these, down\u2010regulation and up\u2010regulation of certain microRNAs crucial for fetal development have been shown to be associated with in utero Pb exposure in human placenta samples. All these modifications in the developing fetus during the prenatal and perinatal stages reportedly caused severe abnormalities in early or adult age, such as impaired growth, obesity, autism, diabetes, cardiovascular diseases, risks of cancer development, and Alzheimer's disease. In this review, currently available information on Pb\u2010mediated alterations in the fetal epigenome is summarized. Further research on Pb\u2010induced epigenome modification will help to understand the mechanisms in detail and will enable us to formulate safety guidelines for pregnant women and developing children.<\/jats:p>","DOI":"10.1002\/jat.4287","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T01:34:56Z","timestamp":1642037696000},"page":"1553-1569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["On\u2010going consequences of in utero exposure of Pb: An epigenetic perspective"],"prefix":"10.1002","volume":"42","author":[{"given":"Fahim Rejanur","family":"Tasin","sequence":"first","affiliation":[{"name":"Biotechnology and Genetic Engineering Discipline Khulna University  Khulna Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-821X","authenticated-orcid":false,"given":"Asif","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Biotechnology and Genetic Engineering Discipline Khulna University  Khulna Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debasish","family":"Halder","sequence":"additional","affiliation":[{"name":"Rare Disease research center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1261-0311","authenticated-orcid":false,"given":"Chanchal","family":"Mandal","sequence":"additional","affiliation":[{"name":"Biotechnology and Genetic Engineering Discipline Khulna University  Khulna Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2012.06.008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheh.2013.04.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.7.3.19183"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2014.06.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2017.1320637"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2608605"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417438111"},{"key":"e_1_2_9_9_1","unstructured":"Bellinger David C&Needleman Herbert L(2003).\u201cIntellectual impairment in children with blood lead concentrations below 10 \u03bcg per deciliter\u201d: Comment."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12427"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2008.02.010"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-009-0109-y"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2014.06.008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.02.012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2013.07.010"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12816"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/cns.15.32"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/jes.2014.26"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1258-4"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2016.06.001"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.10.013"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-015-0131-z"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2012.05.003"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10040274"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a032771"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112304108"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2016.02.002"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/eep\/dvv007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0463-z"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.13.49"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104273"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.29024"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2514"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.2478\/v10102-012-0009-2"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2011.01417.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2018.04.019"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.082701.108"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1293\/tox.2013-0060"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2016.10.014"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0045-7"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.4161\/15592294.2014.989077"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9089101"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10354-012-0074-3"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00310.2010"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/426263"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1510067"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gexplo.2011.06.001"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201100209"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12199-019-0783-y"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.03.017"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2009.04.006"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.5634-10.2011"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2012.00059"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-018-0478-z"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2015.01.037"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00200"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.06.012"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8432-4"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287390490452263"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.10862"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1556\/ABiol.61.2010.2.1"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2015.1066960"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12044"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.11.025"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3504"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1003-6326(14)63052-1"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3430"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12263-013-0354-6"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad-170824"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.3233\/jad-151018"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1146067"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1104474"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.7.2.18764"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2015.05.003"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-9158-3-9"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8743"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22119"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.1.4.3514"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2014.05.007"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/eep\/dvv009"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1515\/reveh-2018-0059"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-009-8479-6"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22311"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00389"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.0800497"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0300-6"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-14792-1_4"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1177\/096032719801700309"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.2478\/intox-2019-0001"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/eep\/dvab005"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2014.12.004"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1515\/reveh.2009.24.1.15"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2016.03.016"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2012.12.004"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1805"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14466"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.12.58"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1367\/1539-4409(2003)003<0037:slpip>2.0.co;2"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.919163"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-019-00547-4"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfs090"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169958"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.07.018"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.31109"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-5-21"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.4.1.7288"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2017.07.002"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1515\/intox-2015-0009"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp1246"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2007.03.021"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3619"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710793205372"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129091"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601630113"},{"key":"e_1_2_9_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2020.111415"},{"key":"e_1_2_9_116_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707442104"},{"key":"e_1_2_9_117_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25175"},{"key":"e_1_2_9_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.03.030"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4287","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jat.4287","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4287","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:50:25Z","timestamp":1760539825000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,24]]},"references-count":117,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/jat.4287"],"URL":"https:\/\/doi.org\/10.1002\/jat.4287","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"value":"0260-437X","type":"print"},{"value":"1099-1263","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,24]]},"assertion":[{"value":"2021-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}