Human embryonic stem cells as a model system for studying the effects of smoke exposure on the embryo.
Human embryonic stem cells (hESCs) share many characteristics including pluripotency with cells of the early embryo and so are potentially useful tools for studying the harmful effects of xenobiotics during early development. Here, we used hESCs as a model system to test the effects of nicotine on the pluripotent population of cells that forms the whole body. Specifically, we exposed hESCs (H7 and H9) to various concentrations of nicotine ranging from 0.1 to 6microM. We evaluated the effects in terms of cell adhesion, integrin expression, hESC colony morphology, markers of pluripotency and survival. The results revealed a significant negative impact of nicotine in the dose range between 1.8 and 3.7microM on all the endpoints analyzed. The observed effects were reversed by the addition of the nicotine antagonist d-tubocurarine, suggesting that the effects are receptor mediated. Together these results offer new explanations in terms of embryo toxicity for the large negative impact of cigarette smoke exposure on a woman's reproductive capacity.
Zdravkovic
Tamara
T
Department of Cell and Tissue Biology, University of California, San Francisco, CA 94143-0512, USA.
Genbacev
Olga
O
LaRocque
Nicholas
N
McMaster
Michael
M
Fisher
Susan
S
D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008954:Models, Biological; D009538:Nicotine / Q000633:toxicity*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*
D015415:Biomarkers; D009538:Nicotine