Adolescent epigenetic profiles and environmental exposures from early life through peri-adolescence.

Abstract

Epigenetic perturbations induced by environmental exposures at susceptible lifestages contribute to disease development. Even so, the influence of early life and ongoing exposures on the adolescent epigenome is rarely examined. We examined the association of exposure biomarkers for lead (Pb), bisphenol A (BPA), and nine phthalates metabolites with blood leukocyte DNA methylation at LINE-1 repetitive elements and environmentally responsive genes ( IGF2 , H19 , and HSD11B2 ) in peri-adolescents. Participants ( n = 247) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohorts were followed-up once between the ages of 8 and 14 years, and concurrent exposures were measured in biospecimen collected at that time (blood Pb, urinary BPA, and phthalate metabolites). Prenatal and childhood exposures to Pb were previously approximated using maternal and child samples. BPA and phthalate metabolites were measured in third trimester maternal urine samples. Significant associations ( P < 0.05) were observed between DNA methylation and exposure biomarkers that were gene and biomarker specific. For example, Pb was only associated with LINE-1 hypomethylation during pregnancy ( P = 0.04), while early childhood Pb was instead associated with H19 hypermethylation ( P = 0.04). Concurrent urinary mono (2-ethylhexyl) phthalate (MEHP) was associated with HSD11B2 hypermethylation ( P = 0.005). Sex-specific associations, particularly among males, were also observed. In addition to single exposure models, principal component analysis was employed to examine exposure mixtures. This method largely corroborated the findings of the single exposure models. This study along with others in the field suggests that environment-epigenetic relationships vary by chemical, exposure timing, and sex.