MONITORING OF GENE EXPRESSION IN DIFFERENTIATION OF EMBRYOID BODIES FROM CYNOMOLGUS MONKEY EMBRYONIC STEM CELLS IN THE PRESENCE OF BISPHENOL A

DOI Web Site Web Site PubMed 参考文献33件 オープンアクセス
  • YAMAMOTO Megumi
    Physiology Section, Department of Basic Medical Sciences, National Institute for Minamata Disease Environmental Health Sciences Division, National Institute for Environmental Studies
  • TASE Naomi
    Tsukuba Primate Research Center, National Institute of Biomedical Innovation
  • OKUNO Tsuyoshi
    Advanced Medical Research Laboratories, Tanabe Seiyaku Co., Ltd.
  • KONDO Yasushi
    Advanced Medical Research Laboratories, Tanabe Seiyaku Co., Ltd.
  • AKIBA Suminori
    Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences
  • SHIMOZAWA Nobuhiro
    Tsukuba Primate Research Center, National Institute of Biomedical Innovation
  • TERAO Keiji
    Tsukuba Primate Research Center, National Institute of Biomedical Innovation

書誌事項

公開日
2007
DOI
  • 10.2131/jts.32.301
公開者
一般社団法人　日本毒性学会

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説明

An embryonic stem (ES) cell differentiation model would facilitate analysis of developmental processes at the cellular level and the effects of embryotoxic and teratogenic factors in vitro. We explored the use of differentiation of embryoid bodies (EBs) from cynomolgus monkey ES cells for embryotoxicity testing. We determined the mRNA expression of various genes using real-time RT-PCR. Oct-3/4 expression was almost completely suppressed on day 14, suggesting that ES cells reached differentiated status in around 14 days. mRNA expression of E-cadherin, connexin 43, caveolin-1, and argininosuccinate synthetase was reproducibly suppressed during EB differentiation in 7−32% of ES cells in three separate experiments. Although these may not be "general stemness marker genes" such as Oct-3/4, they could play a role in readying stem cells for differentiation in response to deletion of signals from feeder cells. Next, we examined the effects of bisphenol A (BPA) on the mRNA expression of several differentiation marker genes for ES cells. That of PAX-6, an ectoderm marker, with 0, 0.1, and 10 μM BPA in 21-day EBs was 3,500%, 6,668%, and 8,394%, respectively, compared with ES cells. The difference between doses of 0 and 10 μM BPA in 21-day EBs was statistically significant (p=0.049). Pax-6 activation in the presence of BPA may interfere with the development of eyes, sensory organs, and certain neural and epidermal tissues usually derived from ectodermal tissues. Differentiation of EBs from cynomolgus monkey ES cells could be a useful model for detecting gene expression changes in response to chemical exposure.<br>

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