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

Ying-Chu Lin⁶  Kung-Kai Kuo¹  Kenly Wuputra²  Shih-Han Lin²  Chia-Chen Ku²  Ya-Han Yang¹  Shin-Wei Wang¹  Sheng-Wen Wang¹  Deng-Chyang Wu¹  Chun-Chien Wu¹  Chee-Yin Chai¹  Cheng-Lung Lin¹  Chang-Shen Lin²  Masayuki Kajitani³  Hiroyuki Miyoshi⁷  Yukio Nakamura⁷  Shinichi Hashimoto⁵  Kouji Matsushima⁵  Chunyuan Jin⁴  Shau-Ku Huang⁸  Shigeo Saito³ 

[1] College of Medicine, Kaohsiung Medical University and Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan; E-Mails:;Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mails:;School of Science and Engineering, Teikyo University, Utsunomiya, Tochigi 329-2192, Japan; E-Mail:;Department of Environmental Medicine, NYU School of Medicine, Tuxedo, NY 10987, USA; E-Mail:;Department of Molecular Preventive Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo 113-8655, Japan; E-Mails:;School of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan;RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan; E-Mails:;Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Rd, Zhunan, Miaoli County 350, Taiwan; E-Mail:

关键词: bovine iPSCs;    testicular cells;    OCT4;    electroporation;    endocrine disruptor;    frizzled receptor;    WNT signal;    androgen receptor;   

DOI  :  10.3390/ijms15035011

来源: mdpi

【 摘 要 】

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 p21^CIP1. The loss of the frizzed receptor 7 and the gain of p21^CIP 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland