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Identification of such development\u2010interfering agents is a challenging task, although multi\u2010angle approaches\u2014including the use of in vitro toxicology studies involving embryonic stem cells\u2014should alleviate some of the current difficulties. In the present study, we utilized the in vitro elongation of embryoid bodies (EBs) derived from mouse embryonal carcinoma stem cell line P19C5 as a model of early embryological events, specifically that of gastrulation and axial patterning. From our study, we identified donepezil, a medication indicated for the management of Alzheimer's disease, as a potential developmental toxicant. The extent of P19C5 EB axial elongation was diminished by donepezil in a dose\u2010dependent manner. Although donepezil is a known inhibitor of acetylcholinesterase, interference of elongation was not mediated through this enzyme. Quantitative reverse\u2010transcriptase PCR revealed that donepezil altered the expression pattern of a specific set of developmental regulator genes involved in patterning along the anterior\u2013posterior body axis. When tested in mouse whole embryo culture, donepezil caused morphological abnormalities including impaired somitogenesis. Donepezil also diminished elongation morphogenesis of EBs generated from human embryonic stem cells. These results suggest that donepezil interferes with axial elongation morphogenesis of early embryos by altering the expression pattern of regulators of axial development. <jats:italic>Mol. Reprod. Dev. 81: 994\u20131008, 2014. \u00a9 2014 Wiley Periodicals, Inc<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mrd.22423","type":"journal-article","created":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T17:23:55Z","timestamp":1412097835000},"page":"994-1008","source":"Crossref","is-referenced-by-count":28,"title":["Morphology\u2010based mammalian stem cell tests reveal potential developmental toxicity of donepezil"],"prefix":"10.1002","volume":"81","author":[{"given":"Caroline G.Y.","family":"Lau","sequence":"first","affiliation":[{"name":"University of Hawaii John A. Burns School of Medicine Honolulu Hawaii"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Marikawa","sequence":"additional","affiliation":[{"name":"University of Hawaii John A. 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