Int. J. Mol. Sci. 2014, 15(3), 5011-5031; doi:10.3390/ijms15035011
Article

Bovine Induced Pluripotent Stem Cells Are More Resistant to Apoptosis than Testicular Cells in Response to Mono-(2-ethylhexyl) Phthalate

Received: 25 January 2014; in revised form: 4 March 2014 / Accepted: 6 March 2014 / Published: 20 March 2014
(This article belongs to the Section Molecular Pathology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: bovine iPSCs; testicular cells; OCT4; electroporation; endocrine disruptor; frizzled receptor; WNT signal; androgen receptor
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MDPI and ACS Style

Lin, Y.-C.; Kuo, K.-K.; Wuputra, K.; Lin, S.-H.; Ku, C.-C.; Yang, Y.-H.; Wang, S.-W.; Wang, S.-W.; Wu, D.-C.; Wu, C.-C.; Chai, C.-Y.; Lin, C.-L.; Lin, C.-S.; Kajitani, M.; Miyoshi, H.; Nakamura, Y.; Hashimoto, S.; Matsushima, K.; Jin, C.; Huang, S.-K.; Saito, S.; Yokoyama, K.K. Bovine Induced Pluripotent Stem Cells Are More Resistant to Apoptosis than Testicular Cells in Response to Mono-(2-ethylhexyl) Phthalate. Int. J. Mol. Sci. 2014, 15, 5011-5031.

AMA Style

Lin Y-C, Kuo K-K, Wuputra K, Lin S-H, Ku C-C, Yang Y-H, Wang S-W, Wang S-W, Wu D-C, Wu C-C, Chai C-Y, Lin C-L, Lin C-S, Kajitani M, Miyoshi H, Nakamura Y, Hashimoto S, Matsushima K, Jin C, Huang S-K, Saito S, Yokoyama KK. 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. 2014; 15(3):5011-5031.

Chicago/Turabian Style

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. 2014. "Bovine Induced Pluripotent Stem Cells Are More Resistant to Apoptosis than Testicular Cells in Response to Mono-(2-ethylhexyl) Phthalate." Int. J. Mol. Sci. 15, no. 3: 5011-5031.

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