Next the investigators looked at genetically engineered COMT deficient mice; as predicted, the animals failed to produce 2-ME. At 14 weeks gestation the presumable equivalent of the beginning of the third trimester in human pregnancy the animals developed protein leak in the urine, high blood pressure and problems with placental blood vessels associated with decreased oxygen levels.
In addition, the animals delivered a day or so earlier than normal pregnant mice and there was a greater incidence of stillborn pups. However, once the pups were delivered, the health of the mother returned to normal.
The loss of 2-ME likely sets in motion a cascade of events culminating in preeclampsia, says Kalluri. Disruption of COMT/2-ME led to elevated hypoxia, leading to angiogenic dysfunction and placental insufficiency, which then results in a further decrease in 2-ME levels.
In the final portion of the study, the authors administered 2-ME to the mice, resulting in a reversal of preeclampsia-like-symptoms.
Interestingly, the many diverse factors that have been identified in the recent years as elevated or suppressed in women with preeclampsia are fixed by 2-ME, suggesting that this action of COMT is central to proper vascular function in the placenta, notes Kalluri. This study offers the possibility of screening for COMT gene defects in pregnant women to predict preeclampsia.
|Contact: Jerry Berger|
Beth Israel Deaconess Medical Center