Necrotic trophoblast debris increases blood pressure during pregnancy

Abstract

Preeclampsia is a major disease of human pregnancy characterised by hypertension and proteinuria. These signs are preceded by systemic maternal endothelial dysfunction. Hypertension in preeclampsia appears to be triggered by a placental factor, which leads to endothelial activation/dysfunction. One potential placental trigger for preeclampsia is necrotic trophoblast cell debris shed from the placenta into maternal blood. The larger trophoblast debris is trapped in the maternal pulmonary vessels and is hypothesised to be cleared by endothelial cells. Phagocytosis of necrotic but not apoptotic trophoblast debris by endothelial cells leads to their activation in vitro. We hypothesised that intravenous injection of necrotic trophoblast debris would induce hypertension in pregnant rats. Virgin female Wistar rats were surgically implanted with telemetry devices to monitor arterial blood pressure and chronic intravenous catheters to allow delivery of necrotic trophoblast debris. After recovery, the rats were mated and, from day 6 of gestation until parturition, they were given five consecutive daily injections per week of 5×106 necrotic Jeg-3 cells per kilo bodyweight. Control rats received vehicle injections. The normalised mean arterial blood pressure of rats receiving injections of necrotic trophoblast debris was higher than control rats during the third week of gestation, while mean arterial blood pressure decreased less from the pre-pregnancy baseline compared to control rats. These results suggest that necrotic trophoblast debris has a hypertensive effect which manifests in late gestation in Wistar rats and supports the theory that necrotic trophoblast debris may trigger the symptoms of preeclampsia.