Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

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 alpha, 4 beta, and 1 delta,gamma and epsilon 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 alpha 2, alpha 3, alpha 4, alpha 9, beta 2 AND beta 4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the alpha 9 subunit, and decreased expression of the delta subunit. At the protein level, expression of both alpha 9 and delta was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically alpha 9 and delta subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (alpha 9), and increased calcification and apoptosis (delta), seen in the placentas of smoking women. (c) 2014 Elsevier Inc. All rights reserved.