The alteration of gene expression mediated by epigenetic modifications, specifically DNA methylation, has been proposed as a mechanism by which chemical and biological factors during gestation and childhood may influence health and adult disease onset. Epigenetics of imprinted genes, which exhibit expression of one parental allele, represent a promising area of fetal programming research, as many imprinted genes are involved in early growth and development.
The aim of the proposed study is to characterize the relationship of prenatal exposure to common endocrine disruptors, phthalates, with DNA methylation of imprinted genes in newborns. The analysis will include DNA samples from the well-characterized CHAMACOS birth cohort study of hundreds of Mexican-American children and their mothers followed from early pregnancy through adolescence. In order to discern relationships between epigenetic profiles of newborns and early life exposure parameters, DNA methylation of imprinted genes in newborns will be assessed using targeted pyrosequencing, followed by validation of the hits by next generation sequencing. DNA methylation of imprinted genes will also be interrogated for associations with biological factors (sex, gestational age, and birth weight), phthalate exposure during pregnancy, and parental obesity. The CHAMACOS study provides a unique opportunity to assess biological and environmental interactions with imprinted gene epigenetics in a cohort with substantial environmental stressors and a high prevalence of parental pre-pregnancy obesity. The research outlined in this proposal will contribute to the limited knowledge regarding the effects of in utero phthalate exposure on methylation of imprinted genes, which thus far includes limited data on only two imprinted genes.7,8 We will expand this analysis to include several additional imprinted genes with high biological significance for fetal development. We will also validate findings of the association between methylation marks and parental obesity from another birth cohort (NEST).9,10 Data generated by the state-of-the art epigenetic and bioinformatic methodologies will provide insights into imprinted gene epigenetics and may identify potential new targets for intervention in pregnant women.
Imprinted genes are involved in early growth and development, and may contribute to later disease risk. This study will evaluate the effects of prenatal exposure to endocrine disruptors such as phthalates, on epigenetic profiles of imprinted genes in newborns from a well-characterized minority birth cohort. Results of the study will provide mechanistic insights into the epigenetic-environment interactions related to imprinted gene methylation profiles, a significant topic for fetal origin of human disease and a high priority for public health research.
|Tindula, Gwen; Murphy, Susan K; Grenier, Carole et al. (2018) DNA methylation of imprinted genes in Mexican-American newborn children with prenatal phthalate exposure. Epigenomics 10:1011-1026|