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Retinoic acid influences the embryoid body formation in mouse embryonic stem cells by induction of caspase and p38 MAPK/JNK-mediated apoptosis

Authors

  • Fu-Jen Huang,

    Corresponding author
    1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
    2. Chang Gung University School of Medicine, Kaohsiung, Taiwan
    • Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
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  • Kuo-Chung Lan,

    1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
    2. Chang Gung University School of Medicine, Kaohsiung, Taiwan
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  • Hong-Yo Kang,

    1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
    2. Chang Gung University School of Medicine, Kaohsiung, Taiwan
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  • Pin-Yao Lin,

    1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
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  • Wen-Hsiung Chan,

    Corresponding author
    1. Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan
    • Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan
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  • Yu-Cheng Hsu,

    1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
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  • Yen-Chih Liu,

    1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
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  • Ko-En Huang

    1. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
    2. Chang Gung University School of Medicine, Kaohsiung, Taiwan
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  • Supported by Chang Gung Memorial Hospital (No. CMRPG850101) and National Science Council of the Republic of China (No. NSC95-2314-B-182A-159-MY3).

Abstract

Although all-trans retinoic acid (RA), the oxidative metabolite of vitamin A, is essential for normal development, high levels are teratogenic in many species. RA results in immediate effects on the preimplantation embryo and on blastocyst development in vitro and in vivo. To further elucidate the cellular mechanisms of early postimplantation embryo development induced by RA, we present an embryonic cell line, B5, as a candidate system for the investigation of these processes. We used undifferentiated ES cells as the model, which is from the undifferentiated status to differentiated status [embryoid body (EB) formation] mimicking postimplantation embryo development (egg-cylinder stage of embryo formation) to clarify the cellular mechanism of action of RA in the implanted blastocysts and cell apoptosis following the series of exposures to differing RA concentrations. Using an in vitro model, we identified the impact of RA on undifferentiated embryonic stem (ES) cells, including inhibition of cell proliferation and induction of cell apoptosis. JNK, P-38 and caspase activation were shown in the nature of RA-triggered apoptotic signaling in ES cells. The carry-on influences of RA on the ES cell were shown in the formation of EB from the pretreated ES cells. RA resulted in apparent impact on undifferentiated ES cells in vitro, with increased numbers of apoptotic cells initially and inhibited cell proliferation, which led to decreased size of EB. The process of EB formation (mimicking the early postimplantation embryo development) is regulated by RA-induced apoptosis through the activation of caspase and P38 MAPK/JNK pathway. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.

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