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HERO ID
4452973
Reference Type
Journal Article
Title
Assessing reproductive toxicity of two environmental toxicants with a novel in vitro human spermatogenic model
Author(s)
Easley, CA; Bradner, JM; Moser, A; Rickman, CA; Mceachin, ZT; Merritt, MM; Hansen, JM; Caudle, WM
Year
2015
Is Peer Reviewed?
1
Journal
Stem Cell Research
ISSN:
1873-5061
Volume
14
Issue
3
Page Numbers
347-355
Language
English
PMID
25863443
DOI
10.1016/j.scr.2015.03.002
Web of Science Id
WOS:000359993400009
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.
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IRIS
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1,2-Dibromo-3-chloropropane
Litsearch 2018
Pubmed
WOS
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