Abstract
This review addresses the general hypothesis that pathogenesis of preeclampsia is
related to an imbalance of increased oxidative stress and lipid peroxidation coupled
a deficiency of antioxidant protection. Evidence will be presented that this imbalance
is present in both the maternal compartment and the placental compartment and that
interactions between these two compartments result in the clinical manifestations
of this disorder. We suggest the following as a scenario for the development of preeclampsia:
Oxidative stress in the maternal compartment affects the placenta in such a way as
to bring about decrease placental antioxidant enzyme protection. The oxidative stress
in the maternal compartment may be preexisting (e.g., obesity, diabetes, hyperlipidemia)
or may be caused by placental secretion of lipid peroxides. Decreased placental antioxidant
enzyme protection leads to a cascade of events in the placenta of uncontrolled lipid
peroxidation with increased thromboxane production and tumor necrosis factor (TNF-α)
production. Increased placental secretion of lipid peroxides and/or TNF-α results
in activation of leukocytes as they circulate through the intervillous space. The
activated leukocytes serve as circulating mediators that link the increased oxidative
stress of the placenta with a widespread increase in oxidative stress and endothelial
dysfunction in the mother. In the third trimester, when the placenta is growing rapidly,
the mother's antioxidant capacity is no longer able to compensate, and the clinical
symptoms of preeclampsia appear.
Keywords:
Lipid peroxides - antioxidants - cytokines - preeclampsia - placenta - leukocytes
