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 HuangShigeo Saito, Kazunari K. Yokoyama

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


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
Pages (from-to)5011-5031
Number of pages21
JournalInternational journal of molecular sciences
Issue number3
Publication statusPublished - Mar 20 2014


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

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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