title: Toxicological effects of the different substances in tobacco smoke on human embryonic development by a systems chemo-biology approach.
abstract: The physiological and molecular effects of tobacco smoke in adult humans and the development of cancer have been well described. In contrast, how tobacco smoke affects embryonic development remains poorly understood. Morphological studies of the fetuses of smoking pregnant women have shown various physical deformities induced by constant fetal exposure to tobacco components, especially nicotine. In addition, nicotine exposure decreases fetal body weight and bone/cartilage growth in addition to decreasing cranial diameter and tibia length. Unfortunately, the molecular pathways leading to these morphological anomalies are not completely understood. In this study, we applied interactome data mining tools and small compound interaction networks to elucidate possible molecular pathways associated with the effects of tobacco smoke components during embryonic development in pregnant female smokers. Our analysis showed a relationship between nicotine and 50 additional harmful substances involved in a variety of biological process that can cause abnormal proliferation, impaired cell differentiation, and increased oxidative stress. We also describe how nicotine can negatively affect retinoic acid signaling and cell differentiation through inhibition of retinoic acid receptors. In addition, nicotine causes a stress reaction and/or a pro-inflammatory response that inhibits the agonistic action of retinoic acid. Moreover, we show that the effect of cigarette smoke on the developing fetus could represent systemic and aggressive impacts in the short term, causing malformations during certain stages of development. Our work provides the first approach describing how different tobacco constituents affect a broad range of biological process in human embryonic development.
authors: Department of Molecular Biology and Biotechnology, Biotechnology Center of the Federal University of Rio Grande do Sul, Federal University of Rio Grande do Sul, Porto Alegre, RS-Brazil.
authors: Bruno César
authors: BC
authors: Feltes
authors: Joice
authors: J
authors: de Faria Poloni
authors: Daniel Luis
authors: DL
authors: Notari
authors: Diego
authors: D
authors: Bonatto
mesh_terms: D001842:Bone and Bones / Q000166:cytology; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D006801:Humans; D009538:Nicotine / Q000633:toxicity; D010084:Oxidation-Reduction / Q000187:drug effects; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism; D060066:Protein Interaction Maps / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis*; D049490:Systems Biology / Q000379:methods*; D014116:Toxicology / Q000379:methods*; D014212:Tretinoin / Q000378:metabolism; D014026:Nicotiana
chemical_list: D011453:Prostaglandins; D012906:Smoke; D014212:Tretinoin; D009538:Nicotine
references: J Cell Physiol. 2010 May;223(2):471-9
references: 20112286
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D1077-81
references: 22064864
references: Mol Cell Biol. 2005 Feb;25(3):1054-69
references: 15657432
references: Oncogene. 2002 Oct 21;21(48):7435-51
references: 12379884
references: Bioinformatics. 2009 Nov 1;25(21):2857-9
references: 19729372
references: Early Hum Dev. 2007 Nov;83(11):699-706
references: 17900829
references: Toxicon. 2004 May;43(6):619-32
references: 15109883
references: Chem Res Toxicol. 2011 Jun 20;24(6):809-17
references: 21452897
references: BMC Bioinformatics. 2003 Jan 13;4:2
references: 12525261
references: Drug Metab Rev. 2006;38(4):791-804
references: 17145702
references: Toxicol Sci. 2011 Aug;122(2):448-56
references: 21602187
references: Dev Dyn. 2012 Apr;241(4):792-802
references: 22374744
references: Hum Reprod Update. 2011 Sep-Oct;17(5):589-604
references: 21747128
references: PLoS One. 2008;3(12):e3945
references: 19079602
references: Fertil Steril. 2011 Jun;95(7):2410-7
references: 21514584
references: Database (Oxford). 2010 Aug 05;2010:baq020
references: 20689021
references: Am J Reprod Immunol. 2011 Jun;65(6):578-88
references: 21223422
references: Bioinformatics. 2009 Jan 15;25(2):288-9
references: 19033274
references: Dev Biol. 1995 Jan;167(1):75-86
references: 7851664
references: Curr Cancer Drug Targets. 2011 Sep;11(7):849-69
references: 21762077
references: Nucleic Acids Res. 2000 Sep 15;28(18):3442-4
references: 10982861
references: Cell Signal. 2005 Oct;17(10):1183-93
references: 15982853
references: Ther Drug Monit. 2009 Feb;31(1):14-30
references: 19125149
references: Dev Biol. 1969 Aug;20(2):146-57
references: 5799427
references: Trends Genet. 1997 Apr;13(4):163
references: 9097728
references: Baillieres Clin Obstet Gynaecol. 1992 Dec;6(4):809-27
references: 1477999
references: Endocr Rev. 2006 Jun;27(4):331-55
references: 16632680
references: Int Rev Cytol. 2007;258:83-136
references: 17338920
references: Chem Rev. 2011 Oct 12;111(10):5866-98
references: 21936577
references: Genome Res. 2003 Nov;13(11):2498-504
references: 14597658
references: Development. 2005 Sep;132(18):4017-27
references: 16123311
references: PLoS Comput Biol. 2007 Apr 20;3(4):e59
references: 17447836
references: Biochem Soc Trans. 2007 Nov;35(Pt 5):1151-5
references: 17956299
references: Bioinformatics. 2009 Jun 1;25(11):1468-9
references: 19369498
references: Cell. 2008 Sep 19;134(6):921-31
references: 18805086
references: Nat Genet. 2004 Jul;36(7):664
references: 15226743
references: Placenta. 2011 Apr;32(4):317-22
references: 21367451
references: Bioinformatics. 2005 Aug 15;21(16):3448-9
references: 15972284
references: Eur J Neurosci. 2011 Nov;34(10):1574-83
references: 22103415
references: Nicotine Tob Res. 2012 Sep;14(9):1073-82
references: 22355075
references: J Chem Inf Comput Sci. 2002 Sep-Oct;42(5):1136-45
references: 12377001
references: Biogerontology. 2011 Aug;12(4):293-308
references: 21380541
references: J Cell Sci. 2002 Nov 15;115(Pt 22):4317-25
references: 12376563
references: Biochim Biophys Acta. 2013 May;1830(5):3267-88
references: 23201197
references: J Cell Physiol. 2007 Mar;210(3):711-9
references: 17133344
references: J Periodontal Res. 2009 Oct;44(5):657-63
references: 19054295
references: Respir Res. 2010 Jan 29;11:13
references: 20113502
references: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references: 10592173
references: Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3264-9
references: 22334649
references: J Bone Miner Res. 2010 Jun;25(6):1305-13
references: 20200934
references: Am J Pathol. 2008 May;172(5):1222-37
references: 18403597
references: Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L109-14
references: 19411310
references: Mol Genet Metab. 2005 Sep-Oct;86(1-2):25-33
references: 16176880
references: J Cell Biochem. 2002;84(2):324-34
references: 11787061
references: Handb Exp Pharmacol. 2009;(192):29-60
references: 19184645
references: Int J Cancer. 2002 May 10;99(2):171-8
references: 11979430
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D412-6
references: 18940858
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D690-8
references: 19906730
references: Reprod Domest Anim. 2009 Oct;44(5):797-804
references: 19032437