Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring
Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two com...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024001612 |
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| author | Rebekah L. Petroff Dana C. Dolinoy Kai Wang Luke Montrose Vasantha Padmanabhan Karen E. Peterson Douglas M. Ruden Maureen A. Sartor Laurie K. Svoboda Martha M. Téllez-Rojo Jaclyn M. Goodrich |
| author_facet | Rebekah L. Petroff Dana C. Dolinoy Kai Wang Luke Montrose Vasantha Padmanabhan Karen E. Peterson Douglas M. Ruden Maureen A. Sartor Laurie K. Svoboda Martha M. Téllez-Rojo Jaclyn M. Goodrich |
| author_sort | Rebekah L. Petroff |
| collection | DOAJ |
| description | Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two common toxicants, the phthalate di(2-ethylhexyl) phthalate (DEHP) and the metal lead (Pb), using a translational paradigm that selected candidate genes from a mouse study and assessed them in four human birth cohorts. Data from mouse offspring developmentally exposed to DEHP, Pb, or control were used to identify genes with sex-specific sites with differential DNA methylation at postnatal day 21. Associations of human infant DNA methylation in homologous mouse genes with prenatal DEHP or Pb were examined with a meta-analysis. Differential methylation was observed on 6 cytosines (adjusted-p < 0.05) and 90 regions (adjusted-p < 0.001). This translational approach offers a unique method that can detect conserved epigenetic differences that are developmentally susceptible to environmental toxicants. |
| first_indexed | 2024-04-24T22:22:12Z |
| format | Article |
| id | doaj.art-250e66bb854f46d58bad6a02891c8046 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-24T22:22:12Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-250e66bb854f46d58bad6a02891c80462024-03-20T06:08:09ZengElsevierEnvironment International0160-41202024-04-01186108575Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspringRebekah L. Petroff0Dana C. Dolinoy1Kai Wang2Luke Montrose3Vasantha Padmanabhan4Karen E. Peterson5Douglas M. Ruden6Maureen A. Sartor7Laurie K. Svoboda8Martha M. Téllez-Rojo9Jaclyn M. Goodrich10Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USAEnvironmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Nutritional Sciences, University of Michigan, Ann Arbor, MI, USAComputational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USAEnvironmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USAEnvironmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USAEnvironmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Nutritional Sciences, University of Michigan, Ann Arbor, MI, USAObstetrics and Gynecology, Wayne State University, Detroit, MI, USAComputational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA; Biostatistics, University of Michigan, Ann Arbor, MI, USAEnvironmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USACenter for Research on Nutrition and Health, National Institute of Public Health, Cuernavaca, MexicoEnvironmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Corresponding author at: 1415 Washington Heights, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two common toxicants, the phthalate di(2-ethylhexyl) phthalate (DEHP) and the metal lead (Pb), using a translational paradigm that selected candidate genes from a mouse study and assessed them in four human birth cohorts. Data from mouse offspring developmentally exposed to DEHP, Pb, or control were used to identify genes with sex-specific sites with differential DNA methylation at postnatal day 21. Associations of human infant DNA methylation in homologous mouse genes with prenatal DEHP or Pb were examined with a meta-analysis. Differential methylation was observed on 6 cytosines (adjusted-p < 0.05) and 90 regions (adjusted-p < 0.001). This translational approach offers a unique method that can detect conserved epigenetic differences that are developmentally susceptible to environmental toxicants.http://www.sciencedirect.com/science/article/pii/S0160412024001612DNA methylationDEHPLead (Pb)Developmental exposuresTranslational toxicologyEpigenetics |
| spellingShingle | Rebekah L. Petroff Dana C. Dolinoy Kai Wang Luke Montrose Vasantha Padmanabhan Karen E. Peterson Douglas M. Ruden Maureen A. Sartor Laurie K. Svoboda Martha M. Téllez-Rojo Jaclyn M. Goodrich Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring Environment International DNA methylation DEHP Lead (Pb) Developmental exposures Translational toxicology Epigenetics |
| title | Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring |
| title_full | Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring |
| title_fullStr | Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring |
| title_full_unstemmed | Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring |
| title_short | Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring |
| title_sort | translational toxicoepigenetic meta analyses identify homologous gene dna methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring |
| topic | DNA methylation DEHP Lead (Pb) Developmental exposures Translational toxicology Epigenetics |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024001612 |
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