Abstract
Preeclampsia affects 2% to 8% of pregnancies worldwide and results in significantly high maternal and perinatal morbidity and mortality, with delivery being the only definitive treatment. It is not a single disorder, but rather a manifestation of an insult(s) to the uteroplacental unit -whether maternal, fetal, and/or placental. Multiple etiologies have been implicated, including uteroplacental ischemia, maternal infection and/or inflammation, maternal obesity, sleep disorders, hydatidiform mole, maternal intestinal dysbiosis, autoimmune disorders, fetal diseases, breakdown of maternal-fetal immune tolerance, placental aging, and endocrine disorders. Early- and late-onset preeclampsia are associated with different etiologies: early-onset preeclampsia develops because of poor placentation, while late-onset preeclampsia occurs in women with latent maternal endothelial dysfunction. In preeclamptic placentas, acquired, genetic, and immune risk factors may result in impaired trophoblast invasion and spiral artery remodeling, which affects uteroplacental perfusion. The resulting placental hypoxia affects the heme oxygenase system-a known stress response pathway affected by hypoxia that is important during normal pregnancy and may offer a therapeutic approach in preeclampsia. This review will address the effect of the heme oxygenase/carbon monoxide system on the placenta and preeclampsia.