Ubiquitous Flame-Retardant Toxicants Impair Spermatogenesis in a Human Stem Cell Model.

• Type of Material: Article
• Authors: Alyse N. Steves, Emory University; Joshua M. Bradner, Emory University; Kristen L. Fowler, University of Georgia; Danielle Clarkson-Townsend, Emory University; Brittany J. Gill, University of Georgia; Adam C. Turry, University of Georgia; William Michael Caudle, Emory University; Gary W Miller, Emory University; Anthony Chan, Emory University; Charles A. Easley IV, University of Georgia
• Language: English
• Date: 2018-05-25
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.isci.2018.04.014
• Title of Journal or Parent Work: iScience
• ISSN: 2589-0042
• Volume: 3
• Start Page: 161
• End Page: 176
• Grant/Funding Information: This work was supported by the National Science Foundation [DGE-1444932] to A.S., the National Institutes of Health [1K22 ES025418-01] to C.E., Emory University's Atlanta Clinical & Translational Science Institute and University Research Committee (ACTSI/URC) award to C.E., and the NIH [P30 ES019776-01-A1] to G.M.
• Research Categories: Biology, Genetics; Biology, Molecular

Abstract

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.