Research Project
10203208
Project Summary The universally present environmental pollutant benzo[a]pyrene (BaP) has been recently described as transgenerational bone toxicant. Average human exposure doses induced skeletal and cardiovascular defects in the ancestrally exposed offspring in fish models. Cross-generational inheritance of disease susceptibilities in response to environmental stressors is of current concern and needs to be addressed to re-assess the population risk for various diseases, such as cancer, diabetes, osteoporosis or cardiovascular impairments. However, the understanding of the underlying mechanisms, affected molecular pathways and their subsequent impacts on the offspring is not yet conclusive. Deciphering the role of DNA methylation and histone marks in phenotype inheritance is imperative to address the next generations? health. The long-term goal is preventive and therapeutic tool development to better assess, avert, and mitigate osteoporotic fracture risks, eventually reducing human disease susceptibilities due to parental exposures to environmental pollutants. This project is designed to address the central hypothesis that parental BaP-exposure deregulates osteoblast gene expression during critical windows of cell differentiation through a modified DNA methylation profile. To test this hypothesis, parental BaP- exposure induced methylation pattern (SA2) and miRNA level changes (SA1), and the developmental onset of adult bone impairment (SA1) will be studied in three different osteoblast subpopulations. The characterization of the genetic and epigenetic profile of the osteoblast cells at different maturation stages will allow to pinpoint critical windows for later bone mineral density impairment employing the unique medaka fish bone model. This study aligns closely with NIEHS mandate to advance environmental health sciences through enhanced understanding of molecular pathways targeted by environmental pollutants. Discriminating epigenetic marks and genes associated with cross-generational toxicology, the proposed research provides a platform for the development of prognostic/diagnostic tools to identify the risks of adverse effects of parental chemical exposure. Further, this study, in alignment with the goal of the AREA program, provides a unique opportunity for undergraduate students of a minority serving institution to gain research experience in the field of biomedical sciences.
