Carbon monoxide inhibits hypoxia/reoxygenation-induced apoptosis and secondary necrosis in syncytiotrophoblast.
Pre-eclampsia, a hypertensive disorder of pregnancy, affects 5 to 7% of pregnancies. Oxidative stress-induced placental injury and subsequent release of placental debris into the maternal circulation are key pathogenic events in the progression of pre-eclampsia. Women who smoke cigarettes throughout pregnancy are 33% less likely to develop this disorder than nonsmoking women. We postulated that elevated carbon monoxide concentrations in serum of smoking women inhibits apoptosis and debris shedding of trophoblast cells exposed to ischemia-reperfusion injury because carbon monoxide has cytoprotective effects on endothelial and smooth muscle cells in culture. This may be responsible for the reduced risk of pre-eclampsia in smoking women. To assess the cytoprotective properties of carbon monoxide within placental tissue, carbon monoxide treatments were administered to in vitro hypoxia/reoxygenation-insulted villous explants cultured from term human placenta. Induction of apoptosis was assessed using molecular and morphological approaches. Placental villous explants treated with carbon monoxide demonstrated 60% less hypoxia/reoxygenation-induced apoptosis in the differentiated syncytiotrophoblast layer compared with untreated explants undergoing a similar insult. In addition, retention of intact syncytial membranes was observed in carbon monoxide-treated explants. These observations indicate that carbon monoxide has potent antiapoptotic properties within human placenta and may hold therapeutic potential in the treatment of pre-eclampsia.
Bainbridge
Shannon A
SA
Department of Anatomy, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada, K7L 2V7.
Belkacemi
Louiza
L
Dickinson
Michelle
M
Graham
Charles H
CH
Smith
Graeme N
GN
D017209:Apoptosis / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D021041:Placental Circulation / Q000187:drug effects; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D012907:Smoking / Q000378:metabolism* / Q000473:pathology; D014327:Trophoblasts / Q000378:metabolism* / Q000648:ultrastructure
D002248:Carbon Monoxide