Immunohistochemical Expression of the Alpha Nicotinic Acetylcholine Receptor 7 in the Human Normal, Diabetic, and Preeclamptic Placenta and Products of Conception

Abstract

Preeclampsia (PE) and gestational diabetes (GD) are complications in advanced pregnancy while miscarriage for early pregnancy. However, the etiological factors are not well understood. Smoking has been associated with these complications as well as the sudden intrauterine deaths, sudden infant death, miscarriages, and still births. However, the immunolocalization of alpha 7 nicotine acetylcholine receptor (α7-nAChR) is not studied.Materials and Methods: α7-nAChR subunit expression was evaluated in 10 paraffin-embedded placental tissues after delivery and 10 tissue samples of products of conception during first trimester by immunohistochemistry. Among the placental tissues, two samples were normal placental tissue, four from PE mother, and four from GD mother. The expression of α7-nAChR was compared between the two groups in general and within the subgroups of placenta as well. Protein expression was evaluated using the nuclear labeling index (%) of villi with positive cells stained, positive cells in the decidua, and intensity of staining in the outer villous trophoblast layer.Results: The expression of α7-nAChR protein was high in all the cases of placenta and products of conception (POCs). α7-nAChR expression showed no notable differences among different cases of miscarriages irrespective of the mother’s age and gestational age at which the event occurred. However, there were some changes among the normal, PE, and GD placental groups in the linings of the blood vessels. Changes were restricted to the villi (as opposed to the decidua) lining cells, both cytotrophoblast and syncytiotrophoblast, and were specific to the α7 subunit. PE blood vessel lining was thicker and showed more expression of this receptor in endothelial cells and myofibroblasts in PE and GD groups. In POCs, the strong expression was observed in the decidua myocytes of maternal blood vessels and in syncytiotrophoblast and cytotrophoblast of chronic villi.Conclusion: Nicotine acetyl choline receptors are found to be expressed highly in the placental tissues and in products of conception. They may be associated with the sudden perinatal deaths and miscarriages or complications of pregnancy.

The Effect of Gestational Diabetes on the α7 and α4 Subtypes of nAChRs in Human Placenta

“…It should be mentioned that nAChRs-mediated entrance of Ca2+ ions into cells could be considered as one of the main reasons for such gene expression changes, since it can activate the cAMP response element-binding protein (CREB) [26]. As well, GDM-induced hypoxia leads to the thickening of the lining of blood vessels in the placenta that can justify more expressions of the studied receptors in endothelial cells [27]. In another study, Machaalani et al in 2015 showed that nAChR subtypes increase in the pre-eclamptic placenta.…”

Application progress of RVG peptides to facilitate the delivery of therapeutic agents into the central nervous system

“…RVG can specifically recognize receptors on the surface BBB-specific receptor (such as nAChR 29,30 or γ-aminobutyric acid receptor 27 ) to deliver carriers into the CNS in a non-invasive way. The detection results showed that nAChR exists not only in the neuron but also in microglia, 31 such as endothelial cells 32 and Schwann cell. 33 However, RVG only infects neurons, not glial cells.…”