Expression of Endothelin-1 in Human Placenta of Active Smokers: An Immunohistochemical Study

Smoking during pregnancy is very well acknowledged to increase the risk of vascular complications in otherwise low-risk women (Quinton et al., 2008). Smoking also increases the risk of preterm birth, placental abruption and placenta praevia in uncomplicated pregnancies. Prenatal exposure to smoking in pregnant women increases the risk of delivering babies with Low Birth-weight (LBW), intrauterine growth restriction (IUGR) (Huang et al., 2017) and causes perinatal morbidity and mortality (Salafia and Shiverick, 1999; Quinton et al., 2008). The placenta is a highly specialized organ that supports the exchange of nutrients and waste products between maternal and fetal circulatory system. In addition, placenta secretes a large number of hormones and peptides, which help in regulation of feto-placental circulation, maternal health and fetal outcome (Gude et al., 2004). In normal pregnancy, the placental vasculature is dilated to its maximum capacity to permit optimal exchange between mother and the fetus. Towards the end of pregnancy, stimulation of local autacoids enhances vasoconstriction as well as vasodilation leading to normal delivery of the baby. Long acting autacoids such as endothelins have been implicated for mediating sustained vasoconstriction (To, 2012; Carter and Myatt, 1995). Among these, endothelins are recently discovered endothelium derived peptides, which show potent contractile effects in vascular and visceral smooth muscles. Out of the three different isoforms (ET-1, ET-2 and ET-3), Endothelin-1 (ET-1) is the most potent vasoconstrictor compound (Masaki and Yanagisawa, 1992). It is a peptide having 21 amino acids, which was first isolated and sequenced from the supernatant of cultured porcine aortic endothelial cells (Yanagisawa et al., 1988). The effects Abstract: Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide secreted by placenta. Its localization in placental tissue of smoking women has been scarcely reported. In this study, ET-1 expression was examined and compared with that of CD-31 (endothelial cell marker) in the placenta of non-smoking and active smoking women using Avidin-Biotin-Complex (ABC) developer kit. ET-1 immunoreactivity was widely distributed in the small and medium sized capillaries and venules in placental villi of both the groups. The distribution of ET-1 in placental villi was similar to the distribution of CD-31. It was finely granular, dark brown in color and the product of immunoreaction was localized in the cytoplasm of endothelial cells lining the capillaries of placental villi. Specific and high affinity binding sites for ET-1 in placental endothelial cells were noticed in both the groups. No difference was discernible in the distribution pattern of ET-1 in placental villi between smokers and non-smokers group but the ET-1 immunoreactivity in placenta of active smokers was consistently observed to be more intense as compared to non-smokers' placenta. Thus, it is thought that exposure to tobacco during pregnancy may influence the production of ET-1 by endothelial cells in human placenta. Consequently, it is presumed that during pregnancy, the production of ET-1 may be upregulated in the placenta of active smokers which might be responsible for the adverse outcomes of pregnancy due to tobacco exposure.