Detrimental effects of flame retardant, PBB153, exposure on sperm and future generations

• Type of Material: Article
• Authors: Katherine Watkins Greeson, University of Georgia; Kristen L. Fowler, Emory University; Paige M. Estave, University of Georgia; S. Kate Thompson, University of Georgia; Chelsea Wagner, University of Texas Health Science Center; R. Clayton Edenfield, University of Georgia; Krista M. Symosko, University of Georgia; Alyse N. Steves, Yerkes National Primate Research Center; Elizabeth M. Marder, Emory University; Metrecia L. Terrell, Emory University; Hillary Barton, Emory University; Michael Koval, Emory University; Michele Marcus, Emory University; Charles Easley IV, Emory University
• Language: English
• Date: 2020-05-22
• Publisher: Nature Research
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-020-65593-x
• Title of Journal or Parent Work: Scientific Reports
• Volume: 10
• Issue: 1
• Start Page: 8567
• End Page: 8567
• Grant/Funding Information: This work was kindly supported by the National Institutes of Health NIEHS K22ES025418 to C.A.E., R01ES025775 and R24ES028528 to M.M., and NIEHS center grant P30ES019776.
• Keywords: Polybrominated biphenyls; Women; In-utero; Michigan; DNA Methylation; Spermatogenesis; Polychlorinated biphenyls; Science & Technology; Breast cancer; Science & Technology - Other Topics; Toxicants; Multidisciplinary Sciences; Cohort
• Research Categories: Health Sciences, Public Health; Health Sciences, Oncology; Biology, Genetics; Biology, Cell

Abstract

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.