{Reference Type}: Journal Article
{Title}: Translational toxicoepigenetic Meta-Analyses identify homologous gene DNA methylation reprogramming following developmental phthalate and lead exposure in mouse and human offspring.
{Author}: Petroff RL;Dolinoy DC;Wang K;Montrose L;Padmanabhan V;Peterson KE;Ruden DM;Sartor MA;Svoboda LK;Téllez-Rojo MM;Goodrich JM;
{Journal}: Environ Int
{Volume}: 186
{Issue}: 0
{Year}: 2024 Apr 11
{Factor}: 13.352
{DOI}: 10.1016/j.envint.2024.108575
{Abstract}: 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.