Autor: |
Greeson KW; Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA., Fowler KL; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA., Estave PM; Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA., Kate Thompson S; Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA., Wagner C; Department of Obstetrics, Gynecology and Reproductive Sciences, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA., Clayton Edenfield R; Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA., Symosko KM; Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, USA.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA., Steves AN; Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA., Marder EM; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Terrell ML; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Barton H; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Koval M; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA., Marcus M; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Easley CA 4th; Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA, USA. cae25@uga.edu.; Regenerative Bioscience Center, University of Georgia, Athens, GA, USA. cae25@uga.edu.; Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Atlanta, GA, USA. cae25@uga.edu. |
Abstrakt: |
In 1973, the Velsicol Chemical Company, which manufactured FireMaster, a brominated flame retardant, and NutriMaster, a nutritional supplement, mistakenly shipped hundreds of pounds of FireMaster to grain mills around Michigan where it was incorporated into animal feed and then into the food chain across the state. An estimated 6.5 million Michigan residents consumed polybrominated biphenyl (PBB)-laced animal products leading to one of the largest agricultural accidents in U.S. history. To date, there have been no studies investigating the effects of PBB on epigenetic regulation in sperm, which could explain some of the endocrine-related health effects observed among children of PBB-exposed parents. Fusing epidemiological approaches with a novel in vitro model of human spermatogenesis, we demonstrate that exposure to PBB153, the primary component of FireMaster, alters the epigenome in human spermatogenic cells. Using our novel stem cell-based spermatogenesis model, we show that PBB153 exposure decreases DNA methylation at regulatory elements controlling imprinted genes. Furthermore, PBB153 affects DNA methylation by reducing de novo DNA methyltransferase activity at increasing PBB153 concentrations as well as reducing maintenance DNA methyltransferase activity at the lowest tested PBB153 concentration. Additionally, PBB153 exposure alters the expression of genes critical to proper human development. Taken together, these results suggest that PBB153 exposure alters the epigenome by disrupting methyltransferase activity leading to defects in imprint establishment causing altered gene expression, which could contribute to health concerns in the children of men exposed to PBB153. While this chemical is toxic to those directly exposed, the results from this study indicate that the epigenetic repercussions may be detrimental to future generations. Above all, this model may be expanded to model a multitude of environmental exposures to elucidate the effect of various chemicals on germline epigenetics and how paternal exposure may impact the health of future generations. |