Ubiquitous Flame-Retardant Toxicants Impair Spermatogenesis in a Human Stem Cell Model
Alyse N. Steves,
Joshua M. Bradner,
Kristen L. Fowler,
Danielle Clarkson-Townsend,
Brittany J. Gill,
Adam C. Turry,
W. Michael Caudle,
Gary W. Miller,
Anthony W.S. Chan,
Charles A. Easley, IV
Affiliations
Alyse N. Steves
Genetics and Molecular Biology Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA
Joshua M. Bradner
Department of Environmental Health Science, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
Kristen L. Fowler
Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA
Danielle Clarkson-Townsend
Department of Environmental Health Science, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
Brittany J. Gill
Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA
Adam C. Turry
Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA
W. Michael Caudle
Department of Environmental Health Science, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
Gary W. Miller
Department of Environmental Health Science, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
Anthony W.S. Chan
Genetics and Molecular Biology Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, GA 30322, USA; Department of Human Genetics, Emory University, Atlanta, GA 30322, USA
Charles A. Easley, IV
Department of Environmental Health Science, College of Public Health, University of Georgia, Athens, GA 30602, USA; Regenerative Bioscience Center, University of Georgia, Athens, GA 30602, USA; Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, GA 30322, USA; Corresponding author
Summary: Sperm counts have rapidly declined in Western males over the past four decades. This rapid decline remains largely unexplained, but exposure to environmental toxicants provides one potential explanation for this decline. Flame retardants are highly prevalent and persistent in the environment, but many have not been assessed for their effects on human spermatogenesis. Using a human stem cell-based model of spermatogenesis, we evaluated two major flame retardants, hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA), under acute conditions simulating occupational-level exposures. Here we show that HBCDD and TBBPA are human male reproductive toxicants in vitro. Although these toxicants do not specifically affect the survival of haploid spermatids, they affect spermatogonia and primary spermatocytes through mitochondrial membrane potential perturbation and reactive oxygen species generation, ultimately causing apoptosis. Taken together, these results show that HBCDD and TBBPA affect human spermatogenesis in vitro and potentially implicate this highly prevalent class of toxicants in the decline of Western males' sperm counts. : Flame Retardant; Toxicology; Male Reproductive Endocrinology; Stem Cells Research Subject Areas: Flame Retardant, Toxicology, Male Reproductive Endocrinology, Stem Cells Research
