title: Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta.
abstract: Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women.
authors.affiliation: Department of Medicine, The University of Sydney, NSW 2006, Australia; Bosch Institute, The University of Sydney, NSW 2006, Australia; The Children's Hospital at Westmead, NSW 2145, Australia. Electronic address: rita.machaalani@sydney.edu.au.
authors.forename: R
authors.initials: R
authors.lastname: Machaalani
authors.affiliation: Bosch Institute, The University of Sydney, NSW 2006, Australia; School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Ghazavi
authors.affiliation: School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Hinton
authors.affiliation: Department of Medicine, The University of Sydney, NSW 2006, Australia; The Children's Hospital at Westmead, NSW 2145, Australia.
authors.forename: K A
authors.initials: KA
authors.lastname: Waters
authors.affiliation: School of Medicine, University of Western Sydney, NSW 2751, Australia; Heart Research Institute, 7 Eliza St Newtown, NSW 2042, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Hennessy
mesh_terms: D003367:Cotinine / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D003367:Cotinine
keywords: Infant; Nicotine; Protein; Tissue and serum cotinine; Tobacco smoke; mRNA