The unfolded protein response and apoptotic regulation in the human placenta due to maternal cigarette smoking and pre-eclampsia

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 105; pp. 120 - 127
• Main Authors: Thomson, S., Waters, K.A., Hennessy, A., Machaalani, R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2021
• Subjects: Activating Transcription Factor 6 - metabolism; Adult; Apoptosis; Cell death; Cigarette Smoking - metabolism; eIF-2 Kinase - metabolism; Endoribonucleases - metabolism; Female; Humans; NF-KappaB Inhibitor alpha - metabolism; Nicotine; PERK; Placenta - metabolism; Pre-eclampsia; Pre-Eclampsia - metabolism; Pregnancy; Protein folding; Protein Serine-Threonine Kinases - metabolism; Unfolded Protein Response; UPR; SIDS; IHC; JNK; BiP; PARP; PERK; BCL-2; TAK1; OD; Protein folding; nAChR; UPR; IRE1; BAD; Pre-eclampsia; MAPK; ER; SAPK; CS; eIF2α; ERAD; CHK2; PE; Cell death; HSP27; ATF6; ERK; Nicotine
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2021.09.001

•Unfolded protein response markers are not altered in cigarette exposed placenta.•Preeclamptic (PE) placentas had higher pPERK in decidua & villi, and IRE1 in villi.•Apoptotic inhibitor IκBα(Ser32/36) was lower in cigarette exposed & PE placentas.
Maternal cigarette smoking (CS) and pre-eclampsia (PE) alter placental function and expression of important proteins which maintain homeostasis. Two interlinked pathways of interest are the unfolded protein response (UPR) and apoptosis. The UPR is upregulated in the PE placenta, but no data is available on the effects of CS and how it correlates with apoptotic expression. Samples of human placental tissue from normotensive non-smokers (n = 8), women with PE (n = 8), and CS (n = 8) were analysed using immunohistochemistry for 3 UPR markers (phosphorylated PKR-like endoplasmic reticulum (ER) kinase (pPERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6)), and an antibody microarray for 19 apoptotic and stress regulating markers. For the PE group compared to the normotensive group, staining for pPERK was increased in decidual tissue and villi, and for IRE1, the overall percentage of stained villi per field of view was increased. There were no differences in UPR expression comparing CS to controls. Of the apoptotic markers, only IκBα (Ser32/36), which is part of an inhibitory pathway, showed a significant decrease in the PE and CS groups compared to controls. These findings suggest UPR regulation is more evident in PE with a general increase in ER stress due to decreased inhibition of apoptosis as compared to CS for which UPR was not altered.