Human embryonic stem cells as a model system for studying the effects of smoke exposure on the embryo

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 26; no. 2; pp. 86 - 93
• Main Authors: Zdravkovic, Tamara, Genbacev, Olga, LaRocque, Nicholas, McMaster, Michael, Fisher, Susan
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-10-2008; Elsevier
• Subjects: Adhesion; Apoptosis - drug effects; Biological and medical sciences; Biomarkers - metabolism; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Cell Line; Dose-Response Relationship, Drug; Embryology: invertebrates and vertebrates. Teratology; Embryonic Development - drug effects; Embryonic Stem Cells - cytology; Embryonic Stem Cells - drug effects; Embryonic Stem Cells - metabolism; Embryonic Stem Cells - pathology; Fundamental and applied biological sciences. Psychology; Human embryonic stem cells; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Integrin; Maternal smoking; Medical sciences; Models, Biological; Nicotine; Nicotine - toxicity; OCT-3/4; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - drug effects; Pluripotent Stem Cells - metabolism; Pluripotent Stem Cells - pathology; Smoking - adverse effects; Teratology. Teratogens; Tobacco, tobacco smoking; Toxicology; Human embryonic stem cells; Integrin; Adhesion; OCT-3/4; Nicotine; Maternal smoking; Human; Embryo; Stem cell; Cell adhesion molecule; Transcription factor Oct4; Alkaloid; Mother; Embryonic cell; Passive smoking; Models
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2008.07.004

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 6
μM. 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 3.7
μM 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.