Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring

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

Environment International (Apr 2024)

Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring

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

Affiliations

Rebekah L. Petroff: Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA
Dana C. Dolinoy: Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Nutritional Sciences, University of Michigan, Ann Arbor, MI, USA
Kai Wang: Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA
Luke Montrose: Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA
Vasantha Padmanabhan: Environmental 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, USA
Karen E. Peterson: Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Nutritional Sciences, University of Michigan, Ann Arbor, MI, USA
Douglas M. Ruden: Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
Maureen A. Sartor: Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA; Biostatistics, University of Michigan, Ann Arbor, MI, USA
Laurie K. Svoboda: Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA; Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA
Martha M. Téllez-Rojo: Center for Research on Nutrition and Health, National Institute of Public Health, Cuernavaca, Mexico
Jaclyn M. Goodrich: Environmental 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.

Journal volume & issue: Vol. 186
p. 108575

Abstract

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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.

Published in Environment International

ISSN: 0160-4120 (Print)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/environment-international

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