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Review
. 2014 Mar 12;21(2):T1-12.
doi: 10.1530/ERC-13-0360. Print 2014 Apr.

Actions of endocrine-disrupting chemicals on stem/progenitor cells during development and disease

Elizabeth Kopras  1 , Veena Potluri, Mei-Ling Bermudez, Karin Williams, Scott Belcher, Susan Kasper
Affiliations
Review

Actions of endocrine-disrupting chemicals on stem/progenitor cells during development and disease

Elizabeth Kopras et al. Endocr Relat Cancer. .

Abstract

Development and fate of the stem cell are regulated by extrinsic signals from the environment. Endocrine-disrupting chemicals which perturb hormonal signaling in utero and during early childhood may cause deregulation of multiple developmental processes, ranging from breakdown of stem cell niche architecture, developmental reprograming and altered stem cell fate to impaired organ and gonad development and sexual differentiation. Therefore, study of the environmental effects on stem cell integrity and normal development is a new and emerging focus for developmental biologists and cell toxicologists. When combined with new human and mouse stem cell-based models, stem cell differentiation dynamics can be studied in more biologically relevant ways. In this study, we review the current status of our understanding of the molecular mechanisms by which endocrine disruptors alter embryonic stem cell and adult stem/progenitor cell fate, organ development, cancer stem cell activity, and tumorigenesis.

Keywords: cancer stem cell; endocrine disruptors; organ development; stem cell/progenitor cell; steroid hormone receptors.

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Conflict of interest statement

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the review.

Figures

Figure 1
Figure 1
Schematic representation of stem, progenitor, and cancer stem cells and the primary organ systems which are susceptible to EDC exposure. Abbreviations for the specific endocrine disruptors modulating each cell type and organ system are listed as indicated. The chemical names for these abbreviations are provided in the text of the manuscript.
Figure 2
Figure 2
EDCs which disrupt germ cell niche homeostasis. Production of androgens by Leydig cells is downregulated by plasticizers (DEHP) (Zhang et al. 2008). The process of spermatogenesis is disrupted by estrogenic compounds (BPA, E2), preservatives (paraben), and organophosphates (TOCP, SCOTP) (Ahn et al. 2012, Aoki & Takada 2012, Chen et al. 2012). The physical contacts between Sertoli cells and germ cells are broken by exposure to plasticizers (DEHP, MEHP), resulting in premature loss of germ cells (Yao et al. 2010, Erkekoglu et al. 2012). The dicarboximide fungicide Vinclozolin is reported to induce epigenetic transgenerational changes in the sperm epigenome and to cause Leydig cell tumors in rats (Kavlock & Cummings 2005, Guerrero-Bosagna et al. 2012).
See this image and copyright information in PMC

References

    1. Ahn HJ, An BS, Jung EM, Yang H, Choi KC & Jeung EB 2012. Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats. Molecular Reproduction and Development 79 626–636. (doi: 10.1002/mrd.22070) - DOI - PubMed
    1. Annab LA, Bortner CD, Sifre MI, Collins JM, Shah RR, Dixon D, Karimi Kinyamu H & Archer TK 2012. Differential responses to retinoic acid and endocrine disruptor compounds of subpopulations within human embryonic stem cell lines. Differentiation 84 330–343. (doi: 10.1016/j.diff.2012.07.006) - DOI - PMC - PubMed
    1. Aoki T & Takada T 2012. Bisphenol A modulates germ cell differentiation and retinoic acid signaling in mouse ES cells. Reproductive Toxicology 34 463–470. (doi: 10.1016/j.reprotox.2012.06.001) - DOI - PubMed
    1. Biemann R, Navarrete Santos A, Navarrete Santos A, Riemann D, Knelangen J, Bluher M, Koch H & Fischer B 2011. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows. Biochemical and Biophysical Research Communications 417 747–752. (doi: 10.1016/j.bbrc.2011.12.028) - DOI - PubMed
    1. Birnbaum LS 2013. When environmental chemicals act like uncontrolled medicine. Trends in Endocrinology and Metabolism 24 321–323. (doi: 10.1016/j.tem.2012.12.005) - DOI - PMC - PubMed

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