Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human Mesenchymal stem cells

Amy L. Strong, Zhenzhen Shi, Michael J. Strong, David F B Miller, Douglas B. Rusch, Aaron M. Buechlein, Erik K. Flemington, John A. McLachlan, Kenneth Nephew, Matthew E. Burow, Bruce A. Bunnell

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear.

Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology.

Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs.

Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells.

Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalEnvironmental Health Perspectives
Volume123
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Endocrine Disruptors
DDT
Mesenchymal Stromal Cells
RNA Sequence Analysis
Stem Cells
Core Binding Factors
Glucose Transporter Type 4
Osteonectin
Gene Expression
Untranslated RNA
Adult Stem Cells
Lipoprotein Lipase
PPAR gamma
Osteosarcoma
Leptin
Oncogenes
Estrogen Receptors
Cell Biology
Estrogens

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

Strong, A. L., Shi, Z., Strong, M. J., Miller, D. F. B., Rusch, D. B., Buechlein, A. M., ... Bunnell, B. A. (2015). Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human Mesenchymal stem cells. Environmental Health Perspectives, 123(1), 42-48. https://doi.org/10.1289/ehp.1408188

Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human Mesenchymal stem cells. / Strong, Amy L.; Shi, Zhenzhen; Strong, Michael J.; Miller, David F B; Rusch, Douglas B.; Buechlein, Aaron M.; Flemington, Erik K.; McLachlan, John A.; Nephew, Kenneth; Burow, Matthew E.; Bunnell, Bruce A.

In: Environmental Health Perspectives, Vol. 123, No. 1, 2015, p. 42-48.

Research output: Contribution to journalArticle

Strong, AL, Shi, Z, Strong, MJ, Miller, DFB, Rusch, DB, Buechlein, AM, Flemington, EK, McLachlan, JA, Nephew, K, Burow, ME & Bunnell, BA 2015, 'Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human Mesenchymal stem cells', Environmental Health Perspectives, vol. 123, no. 1, pp. 42-48. https://doi.org/10.1289/ehp.1408188
Strong, Amy L. ; Shi, Zhenzhen ; Strong, Michael J. ; Miller, David F B ; Rusch, Douglas B. ; Buechlein, Aaron M. ; Flemington, Erik K. ; McLachlan, John A. ; Nephew, Kenneth ; Burow, Matthew E. ; Bunnell, Bruce A. / Effects of the endocrine-disrupting chemical DDT on self-renewal and differentiation of human Mesenchymal stem cells. In: Environmental Health Perspectives. 2015 ; Vol. 123, No. 1. pp. 42-48.
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abstract = "Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear.Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology.Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs.Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells.Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs.",
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AU - Buechlein, Aaron M.

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AU - Burow, Matthew E.

AU - Bunnell, Bruce A.

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AB - Background: Although the global use of the endocrine-disrupting chemical DDT has decreased, its persistence in the environment has resulted in continued human exposure. Accumulating evidence suggests that DDT exposure has long-term adverse effects on development, yet the impact on growth and differentiation of adult stem cells remains unclear.Objectives: Human mesenchymal stem cells (MSCs) exposed to DDT were used to evaluate the impact on stem cell biology.Methods: We assessed DDT-treated MSCs for self-renewal, proliferation, and differentiation potential. Whole genome RNA sequencing was performed to assess gene expression in DDT-treated MSCs.Results: MSCs exposed to DDT formed fewer colonies, suggesting a reduction in self-renewal potential. DDT enhanced both adipogenic and osteogenic differentiation, which was confirmed by increased mRNA expression of glucose transporter type 4 (GLUT4), lipoprotein lipase (LpL), peroxisome proliferator-activated receptor gamma (PPARγ), leptin, osteonectin, core binding factor 1 (CBFA1), and FBJ murine osteosarcoma viral oncogene homolog (c-Fos). Expression of factors in DDT-treated cells was similar to that in estrogen-treated MSCs, suggesting that DDT may function via the estrogen receptor (ER)-mediated pathway. The coadministration of ICI 182,780 blocked the effects of DDT. RNA sequencing revealed 121 genes and noncoding RNAs to be differentially expressed in DDT-treated MSCs compared with controls cells.Conclusion: Human MSCs provide a powerful biological system to investigate and identify the molecular mechanisms underlying the effects of environmental agents on stem cells and human health. MSCs exposed to DDT demonstrated profound alterations in self-renewal, proliferation, differentiation, and gene expression, which may partially explain the homeostatic imbalance and increased cancer incidence among those exposed to long-term EDCs.

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