Dissociation of pathophysiology of the placenta and blood pressure phenotype in mouse models of preeclampsia

Preeclampsia (PRE) is present in 5–10% of all pregnancies and is characterized by hypertension and proteinuria. Because the symptoms resolve shortly after delivery, the placenta has been suggested to be involved in this disease. Because of the difficulties encountered trying to study PRE in humans, the development of animal models has been a key element in acquiring knowledge. To confirm the presence of PRE, the blood pressure was measured by telemetry and proteinuria was assessed by a Bradford assay. For placenta collection, females were euthanized at the end of gestation. Placentas were then fixed and paraffin embedded. Histological analysis of preeclamptic placenta showed reduced maternal vascularization compared to controls. In addition, placental fibrin deposition on the maternal side was observed in all PRE models. Thus, these results suggest that these placentas have a reduction in blood flow which could have important impacts on the fetus. Indeed, in the p57 KO mice, KO pups had lower body weights which could be indicative of intra‐uterine growth restriction. In addition, intra‐uterine death was more frequent. However, in the hAGT/hREN mice, although pup size was normal, placental weight was decreased which supports the placental necrosis observed in histological cuts. Also, female body weight at the end of gestation was increased in this model which may suggest systemic oedema. However, in both models, only a modest increase in the mean arterial blood pressure and proteinuria was observed. These results suggest that placenta may not be as important as it was thought in the development of PRE. Indeed, underlying maternal factors may be necessary to potentiate the symptoms normally observed in PRE.