Bovine induced pluripotent stem cells are more resistant to apoptosis than testicular cells in response to mono-(2-ethylhexyl) phthalate

Ying Chu Lin, Kung Kai Kuo, Kenly Wuputra, Shih Han Lin, Chia Chen Ku, Ya Han Yang, Shin Wei Wang, Sheng Wen Wang, Deng Chyang Wu, Chun Chien Wu, Chee Yin Chai, Cheng Lung Lin, Chang Shen Lin, Masayuki Kajitani, Hiroyuki Miyoshi, Yukio Nakamura, Shinichi Hashimoto, Kouji Matsushima, Chunyuan Jin, Shau Ku Huang & 2 others Shigeo Saito, Kazunari K. Yokoyama

Research output: Contribution to journalArticle

Abstract

Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.

Original languageEnglish (US)
Pages (from-to)5011-5031
Number of pages21
JournalInternational Journal of Molecular Sciences
Volume15
Issue number3
DOIs
StatePublished - Mar 20 2014
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
phthalates
stem cells
apoptosis
Cell death
Stem cells
Androgen Receptors
Apoptosis
cells
Testicular Hormones
Bone Morphogenetic Protein 4
Leukemia Inhibitory Factor
Endocrine Disruptors
Electroporation
leukemias
Cyclin-Dependent Kinases
hormones
metabolites
Hormones
promotion

Keywords

  • Androgen receptor
  • Bovine iPSCs
  • Electroporation
  • Endocrine disruptor
  • Frizzled receptor
  • OCT4
  • Testicular cells
  • WNT signal

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)

Cite this

Bovine induced pluripotent stem cells are more resistant to apoptosis than testicular cells in response to mono-(2-ethylhexyl) phthalate. / Lin, Ying Chu; Kuo, Kung Kai; Wuputra, Kenly; Lin, Shih Han; Ku, Chia Chen; Yang, Ya Han; Wang, Shin Wei; Wang, Sheng Wen; Wu, Deng Chyang; Wu, Chun Chien; Chai, Chee Yin; Lin, Cheng Lung; Lin, Chang Shen; Kajitani, Masayuki; Miyoshi, Hiroyuki; Nakamura, Yukio; Hashimoto, Shinichi; Matsushima, Kouji; Jin, Chunyuan; Huang, Shau Ku; Saito, Shigeo; Yokoyama, Kazunari K.

In: International Journal of Molecular Sciences, Vol. 15, No. 3, 20.03.2014, p. 5011-5031.

Research output: Contribution to journalArticle

Lin, YC, Kuo, KK, Wuputra, K, Lin, SH, Ku, CC, Yang, YH, Wang, SW, Wang, SW, Wu, DC, Wu, CC, Chai, CY, Lin, CL, Lin, CS, Kajitani, M, Miyoshi, H, Nakamura, Y, Hashimoto, S, Matsushima, K, Jin, C, Huang, SK, Saito, S & Yokoyama, KK 2014, 'Bovine induced pluripotent stem cells are more resistant to apoptosis than testicular cells in response to mono-(2-ethylhexyl) phthalate', International Journal of Molecular Sciences, vol. 15, no. 3, pp. 5011-5031. https://doi.org/10.3390/ijms15035011
Lin, Ying Chu ; Kuo, Kung Kai ; Wuputra, Kenly ; Lin, Shih Han ; Ku, Chia Chen ; Yang, Ya Han ; Wang, Shin Wei ; Wang, Sheng Wen ; Wu, Deng Chyang ; Wu, Chun Chien ; Chai, Chee Yin ; Lin, Cheng Lung ; Lin, Chang Shen ; Kajitani, Masayuki ; Miyoshi, Hiroyuki ; Nakamura, Yukio ; Hashimoto, Shinichi ; Matsushima, Kouji ; Jin, Chunyuan ; Huang, Shau Ku ; Saito, Shigeo ; Yokoyama, Kazunari K. / Bovine induced pluripotent stem cells are more resistant to apoptosis than testicular cells in response to mono-(2-ethylhexyl) phthalate. In: International Journal of Molecular Sciences. 2014 ; Vol. 15, No. 3. pp. 5011-5031.
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abstract = "Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.",
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T1 - Bovine induced pluripotent stem cells are more resistant to apoptosis than testicular cells in response to mono-(2-ethylhexyl) phthalate

AU - Lin, Ying Chu

AU - Kuo, Kung Kai

AU - Wuputra, Kenly

AU - Lin, Shih Han

AU - Ku, Chia Chen

AU - Yang, Ya Han

AU - Wang, Shin Wei

AU - Wang, Sheng Wen

AU - Wu, Deng Chyang

AU - Wu, Chun Chien

AU - Chai, Chee Yin

AU - Lin, Cheng Lung

AU - Lin, Chang Shen

AU - Kajitani, Masayuki

AU - Miyoshi, Hiroyuki

AU - Nakamura, Yukio

AU - Hashimoto, Shinichi

AU - Matsushima, Kouji

AU - Jin, Chunyuan

AU - Huang, Shau Ku

AU - Saito, Shigeo

AU - Yokoyama, Kazunari K.

PY - 2014/3/20

Y1 - 2014/3/20

N2 - Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.

AB - Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.

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KW - Bovine iPSCs

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KW - Endocrine disruptor

KW - Frizzled receptor

KW - OCT4

KW - Testicular cells

KW - WNT signal

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