View in EDS HTML Full Text PDF Full Text

Effects of Developmental Lead and Phthalate Exposures on DNA Methylation in Adult Mouse Blood, Brain, and Liver: A Focus on Genomic Imprinting by Tissue and Sex.

Saved in:
Bibliographic Details
Title: Effects of Developmental Lead and Phthalate Exposures on DNA Methylation in Adult Mouse Blood, Brain, and Liver: A Focus on Genomic Imprinting by Tissue and Sex.
Authors: Morgan, Rachel K.1, Kai Wang2, Svoboda, Laurie K.1, Rygiel, Christine A.1, Lalancette, Claudia3, Cavalcante, Raymond3, Bartolomei, Marisa S.4, Prasasya, Rexxi4, Neier, Kari1, Perera, Bambarendage P. U.1, Jones, Tamara R.1, Colacino, Justin A.1,5, Sartor, Maureen A.2,6, Dolinoy, Dana C.1,5 ddolinoy@umich.edu
Source: Environmental Health Perspectives. Jun2024, Vol. 132 Issue 6, p067003-1-067003-13. 13p.
Subject Terms: *Pollutants, *Animal experimentation, *Environmental exposure, *Plasticizers, *Lead, *Biomarkers, Sex chromosomes, Maternal exposure, Prenatal exposure delayed effects, Tissues, Genome-wide association studies, Research funding, Brain, DNA methylation, Cerebral cortex, Genes, Mice, Gene expression, Fetal development, Liver, Genetic testing, Sequence analysis, Children
Abstract: BACKGROUND: Maternal exposure to environmental chemicals can cause adverse health effects in offspring. Mounting evidence supports that these effects are influenced, at least in part, by epigenetic modifications. It is unknown whether epigenetic changes in surrogate tissues such as the blood are reflective of similar changes in target tissues such as cortex or liver. OBJECTIVE: We examined tissue- and sex-specific changes in DNA methylation (DNAm) associated with human-relevant lead (Pb) and di(2- ethylhexyl) phthalate (DEHP) exposure during perinatal development in cerebral cortex, blood, and liver. METHODS: Female mice were exposed to human relevant doses of either Pb (32 ppm) via drinking water or DEHP (5 mg/kg-day) via chow for 2 weeks prior to mating through offspring weaning. Whole genome bisulfite sequencing (WGBS) was utilized to examine DNAm changes in offspring cortex, blood, and liver at 5 months of age. Metilene and methylSig were used to identify differentially methylated regions (DMRs). Annotatr and ChIP-enrich were used for genomic annotations and gene set enrichment tests of DMRs, respectively. RESULTS: The cortex contained the majority of DMRs associated with Pb (66%) and DEHP (57%) exposure. The cortex also contained the greatest degree of overlap in DMR signatures between sexes (푛=13 and 8 DMRs with Pb and DEHP exposure, respectively) and exposure types (푛=55 and 39 DMRs in males and females, respectively). In all tissues, detected DMRs were preferentially found at genomic regions associated with gene expression regulation (e.g., CpG islands and shores, 5′ UTRs, promoters, and exons). An analysis of GO terms associated with DMR-containing genes identified imprinted genes to be impacted by both Pb and DEHP exposure. Of these, Gnas and Grb10 contained DMRs across tissues, sexes, and exposures, with some signatures replicated between target and surrogate tissues. DMRs were enriched in the imprinting control regions (ICRs) of Gnas and Grb10, and we again observed a replication of DMR signatures between blood and target tissues. Specifically, we observed hypermethylation of the Grb10 ICR in both blood and liver of Pb-exposed male animals. CONCLUSIONS: These data provide preliminary evidence that imprinted genes may be viable candidates in the search for epigenetic biomarkers of toxicant exposure in target tissues. Additional research is needed on allele- and developmental stage-specific effects, as well as whether other imprinted genes provide additional examples of this relationship. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: GreenFILE
Full text is not displayed to guests.
FullText Links:
  – Type: pdflink
Text:
  Availability: 1
Header DbId: 8gh
DbLabel: GreenFILE
An: 178341754
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Effects of Developmental Lead and Phthalate Exposures on DNA Methylation in Adult Mouse Blood, Brain, and Liver: A Focus on Genomic Imprinting by Tissue and Sex.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Morgan%2C+Rachel+K%2E%22">Morgan, Rachel K.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kai+Wang%22">Kai Wang</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Svoboda%2C+Laurie+K%2E%22">Svoboda, Laurie K.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Rygiel%2C+Christine+A%2E%22">Rygiel, Christine A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lalancette%2C+Claudia%22">Lalancette, Claudia</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Cavalcante%2C+Raymond%22">Cavalcante, Raymond</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Bartolomei%2C+Marisa+S%2E%22">Bartolomei, Marisa S.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Prasasya%2C+Rexxi%22">Prasasya, Rexxi</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Neier%2C+Kari%22">Neier, Kari</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Perera%2C+Bambarendage+P%2E+U%2E%22">Perera, Bambarendage P. U.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Jones%2C+Tamara+R%2E%22">Jones, Tamara R.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Colacino%2C+Justin+A%2E%22">Colacino, Justin A.</searchLink><relatesTo>1,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Sartor%2C+Maureen+A%2E%22">Sartor, Maureen A.</searchLink><relatesTo>2,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Dolinoy%2C+Dana+C%2E%22">Dolinoy, Dana C.</searchLink><relatesTo>1,5</relatesTo><i> ddolinoy@umich.edu</i>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. Jun2024, Vol. 132 Issue 6, p067003-1-067003-13. 13p.
– Name: Subject
  Label: Subject Terms
  Group: Su
  Data: *<searchLink fieldCode="DE" term="%22Pollutants%22">Pollutants</searchLink><br />*<searchLink fieldCode="DE" term="%22Animal+experimentation%22">Animal experimentation</searchLink><br />*<searchLink fieldCode="DE" term="%22Environmental+exposure%22">Environmental exposure</searchLink><br />*<searchLink fieldCode="DE" term="%22Plasticizers%22">Plasticizers</searchLink><br />*<searchLink fieldCode="DE" term="%22Lead%22">Lead</searchLink><br />*<searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Sex+chromosomes%22">Sex chromosomes</searchLink><br /><searchLink fieldCode="DE" term="%22Maternal+exposure%22">Maternal exposure</searchLink><br /><searchLink fieldCode="DE" term="%22Prenatal+exposure+delayed+effects%22">Prenatal exposure delayed effects</searchLink><br /><searchLink fieldCode="DE" term="%22Tissues%22">Tissues</searchLink><br /><searchLink fieldCode="DE" term="%22Genome-wide+association+studies%22">Genome-wide association studies</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Brain%22">Brain</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+methylation%22">DNA methylation</searchLink><br /><searchLink fieldCode="DE" term="%22Cerebral+cortex%22">Cerebral cortex</searchLink><br /><searchLink fieldCode="DE" term="%22Genes%22">Genes</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink><br /><searchLink fieldCode="DE" term="%22Fetal+development%22">Fetal development</searchLink><br /><searchLink fieldCode="DE" term="%22Liver%22">Liver</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+testing%22">Genetic testing</searchLink><br /><searchLink fieldCode="DE" term="%22Sequence+analysis%22">Sequence analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Children%22">Children</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: BACKGROUND: Maternal exposure to environmental chemicals can cause adverse health effects in offspring. Mounting evidence supports that these effects are influenced, at least in part, by epigenetic modifications. It is unknown whether epigenetic changes in surrogate tissues such as the blood are reflective of similar changes in target tissues such as cortex or liver. OBJECTIVE: We examined tissue- and sex-specific changes in DNA methylation (DNAm) associated with human-relevant lead (Pb) and di(2- ethylhexyl) phthalate (DEHP) exposure during perinatal development in cerebral cortex, blood, and liver. METHODS: Female mice were exposed to human relevant doses of either Pb (32 ppm) via drinking water or DEHP (5 mg/kg-day) via chow for 2 weeks prior to mating through offspring weaning. Whole genome bisulfite sequencing (WGBS) was utilized to examine DNAm changes in offspring cortex, blood, and liver at 5 months of age. Metilene and methylSig were used to identify differentially methylated regions (DMRs). Annotatr and ChIP-enrich were used for genomic annotations and gene set enrichment tests of DMRs, respectively. RESULTS: The cortex contained the majority of DMRs associated with Pb (66%) and DEHP (57%) exposure. The cortex also contained the greatest degree of overlap in DMR signatures between sexes (푛=13 and 8 DMRs with Pb and DEHP exposure, respectively) and exposure types (푛=55 and 39 DMRs in males and females, respectively). In all tissues, detected DMRs were preferentially found at genomic regions associated with gene expression regulation (e.g., CpG islands and shores, 5′ UTRs, promoters, and exons). An analysis of GO terms associated with DMR-containing genes identified imprinted genes to be impacted by both Pb and DEHP exposure. Of these, Gnas and Grb10 contained DMRs across tissues, sexes, and exposures, with some signatures replicated between target and surrogate tissues. DMRs were enriched in the imprinting control regions (ICRs) of Gnas and Grb10, and we again observed a replication of DMR signatures between blood and target tissues. Specifically, we observed hypermethylation of the Grb10 ICR in both blood and liver of Pb-exposed male animals. CONCLUSIONS: These data provide preliminary evidence that imprinted genes may be viable candidates in the search for epigenetic biomarkers of toxicant exposure in target tissues. Additional research is needed on allele- and developmental stage-specific effects, as well as whether other imprinted genes provide additional examples of this relationship. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=8gh&AN=178341754
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1289/EHP14074
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 13
        StartPage: 067003-1
    Subjects:
      – SubjectFull: Pollutants
        Type: general
      – SubjectFull: Animal experimentation
        Type: general
      – SubjectFull: Environmental exposure
        Type: general
      – SubjectFull: Plasticizers
        Type: general
      – SubjectFull: Lead
        Type: general
      – SubjectFull: Biomarkers
        Type: general
      – SubjectFull: Sex chromosomes
        Type: general
      – SubjectFull: Maternal exposure
        Type: general
      – SubjectFull: Prenatal exposure delayed effects
        Type: general
      – SubjectFull: Tissues
        Type: general
      – SubjectFull: Genome-wide association studies
        Type: general
      – SubjectFull: Research funding
        Type: general
      – SubjectFull: Brain
        Type: general
      – SubjectFull: DNA methylation
        Type: general
      – SubjectFull: Cerebral cortex
        Type: general
      – SubjectFull: Genes
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Gene expression
        Type: general
      – SubjectFull: Fetal development
        Type: general
      – SubjectFull: Liver
        Type: general
      – SubjectFull: Genetic testing
        Type: general
      – SubjectFull: Sequence analysis
        Type: general
      – SubjectFull: Children
        Type: general
    Titles:
      – TitleFull: Effects of Developmental Lead and Phthalate Exposures on DNA Methylation in Adult Mouse Blood, Brain, and Liver: A Focus on Genomic Imprinting by Tissue and Sex.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Morgan, Rachel K.
      – PersonEntity:
          Name:
            NameFull: Kai Wang
      – PersonEntity:
          Name:
            NameFull: Svoboda, Laurie K.
      – PersonEntity:
          Name:
            NameFull: Rygiel, Christine A.
      – PersonEntity:
          Name:
            NameFull: Lalancette, Claudia
      – PersonEntity:
          Name:
            NameFull: Cavalcante, Raymond
      – PersonEntity:
          Name:
            NameFull: Bartolomei, Marisa S.
      – PersonEntity:
          Name:
            NameFull: Prasasya, Rexxi
      – PersonEntity:
          Name:
            NameFull: Neier, Kari
      – PersonEntity:
          Name:
            NameFull: Perera, Bambarendage P. U.
      – PersonEntity:
          Name:
            NameFull: Jones, Tamara R.
      – PersonEntity:
          Name:
            NameFull: Colacino, Justin A.
      – PersonEntity:
          Name:
            NameFull: Sartor, Maureen A.
      – PersonEntity:
          Name:
            NameFull: Dolinoy, Dana C.
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 06
              Text: Jun2024
              Type: published
              Y: 2024
          Identifiers:
            – Type: issn-print
              Value: 00916765
          Numbering:
            – Type: volume
              Value: 132
            – Type: issue
              Value: 6
          Titles:
            – TitleFull: Environmental Health Perspectives
              Type: main
ResultId 1