title: Assessing reproductive toxicity of two environmental toxicants with a novel in vitro human spermatogenic model.
abstract: Environmental influences and insults by reproductive toxicant exposure can lead to impaired spermatogenesis or infertility. Understanding how toxicants disrupt spermatogenesis is critical for determining how environmental factors contribute to impaired fertility. While current animal models are available, understanding of the reproductive toxic effects on human fertility requires a more robust model system. We recently demonstrated that human pluripotent stem cells can differentiate into spermatogonial stem cells/spermatogonia, primary and secondary spermatocytes, and haploid spermatids; a model that mimics many aspects of human spermatogenesis. Here, using this model system, we examine the effects of 2-bromopropane (2-BP) and 1,2,dibromo-3-chloropropane (DBCP) on in vitro human spermatogenesis. 2-BP and DBCP are non-endocrine disrupting toxicants that are known to impact male fertility. We show that acute treatment with either 2-BP or DBCP induces a reduction in germ cell viability through apoptosis. 2-BP and DBCP affect viability of different cell populations as 2-BP primarily reduces spermatocyte viability, whereas DBCP exerts a much greater effect on spermatogonia. Acute treatment with 2-BP or DBCP also reduces the percentage of haploid spermatids. Both 2-BP and DBCP induce reactive oxygen species (ROS) formation leading to an oxidized cellular environment. Taken together, these results suggest that acute exposure with 2-BP or DBCP causes human germ cell death in vitro by inducing ROS formation. This system represents a unique platform for assessing human reproductive toxicity potential of various environmental toxicants in a rapid, efficient, and unbiased format.
authors: Laboratory of Translational Cell Biology, Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: caeasle@emory.edu.
authors: Charles A
authors: CA
authors: Easley
authors: Department of Environmental Health, Rollins School of Public Heath, Emory University, Atlanta, GA 30322, USA; Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Joshua M
authors: JM
authors: Bradner
authors: Laboratory of Translational Cell Biology, Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Amber
authors: A
authors: Moser
authors: Laboratory of Translational Cell Biology, Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Chelsea A
authors: CA
authors: Rickman
authors: Laboratory of Translational Cell Biology, Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech College of Engineering, Atlanta, GA 30332, USA.
authors: Zachary T
authors: ZT
authors: McEachin
authors: Laboratory of Translational Cell Biology, Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Megan M
authors: MM
authors: Merritt
authors: Division of Pulmonology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Jason M
authors: JM
authors: Hansen
authors: Department of Environmental Health, Rollins School of Public Heath, Emory University, Atlanta, GA 30322, USA; Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: W Michael
authors: WM
authors: Caudle
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D009153:Mutagens / Q000494:pharmacology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013087:Spermatids / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013090:Spermatocytes / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D006842:Hydrocarbons, Brominated; D009153:Mutagens; D017382:Reactive Oxygen Species; C007318:1,2-dibromo-3-chloropropane; C103736:2-bromopropane; D011407:Propane