When Preventing Pre-eclampsia, A Little Carbon Monoxide Goes A Long Way

Pre-eclampsia, a form of pregnancy-associated hypertension, affects 5-7% of pregnancies and poses serious risks for both mother and child. If maternal blood vessels at the placental barrier fail to remodel and adapt to the changing nutrient/oxygen needs of the growing fetus, the maternal blood pressure rises in an effort to improve nutrient delivery. This leads to oxidative stress and damage to the placenta, specifically to the syncytiotrophoblast. When syncytiotrophoblast cells die, they are released into the maternal circulation, initiating a cascade of inflammation that can damage maternal organs.

Interestingly, mothers who smoke cigarettes during pregnancy have a 33% decreased risk of developing pre-eclampsia compared to nonsmokers. New research questions whether the carbon monoxide found in cigarette smoke, and subsequently carried in a smoking mother's blood, may be the cause. Carbon monoxide, which is produced naturally by the body at low levels, possesses vessel-relaxing and cytoprotective activities that may prevent syncytiotrophoblast cell death and the resulting injury to fetus and mother.

Dr. Graeme Smith and colleagues examined this hypothesis using tissue from term human placentas obtained following elective caesarian section from nonsmoking, low-risk women. When cultured tissues were exposed to oxidative stress (hypoxia and re-oxygenation), syncytiotrophoblast cell death occurred. However, when tissues were treated with carbon monoxide, at levels similar to those found in blood of smoking mothers, cell death was significantly reduced. Further, carbon-monoxide-treated tissues did not demonstrate the hallmarks of syncytiotrphoblast cell injury and death, such as condensation of DNA, clumping of nuclei, and separation of cells from the rest of the tissue.

These studies have delineated possible mechanisms behind smoking's protective effects on pre-eclampsia and identified carbon monoxide as a possible treatment modality. The use of carbon monoxide in preventing hypoxia/re-oxygenation injury in organ transplantation underscores its potential usefulness here. Future studies will determine whether carbon monoxide can prevent syncytiotrophoblast death in animal models and whether other approaches similar to carbon monoxide may provide feasible protection.

Finally, while cigarette smoking during pregnancy has been correlated with lowered incidence of pre-eclampsia, any perceived benefit of smoking during pregnancy is outweighed by its risks: premature membrane rupture, preterm delivery, stillbirth, low birth weight, and sudden infant death syndrome.

This work was supported by the Strategic Training Initiative in Research in Reproductive Health Sciences, the Heart and Stroke Foundation of Ontario, and the Canadian Institutes of Health Research.

Work was directed by Dr. Graeme Smith from the Queen's University, Kingston, Ontario, Canada.

Reference: Bainbridge SA, Belkacemi L, Dickinson M, Graham CH, Smith GN. Carbon monoxide inhibits hypoxia/reoxygenation-induced apoptosis and secondary necrosis in syncytiotrophoblast. Am J Pathol 2006 169:774-783.