High blood pressure (hypertension) is one of the most feared and common complications of pregnancy. It can induce preeclampsia (PE), responsible for a third of highly premature births in France. This disease is the second leading cause of death in pregnant women, after postpartum haemorrhage. It is thought to be a result of poor placentation in the first trimester of pregnancy. Since the symptoms of preeclampsia only appear by the third trimester of pregnancy, it is currently impossible to diagnose patients early in their pregnancy, or to predict the occurrence of this condition by measuring specific biomarkers.
For the past decade or so, scientists from CEA-BIG have been working on the placental factor related to the EG-VEGF protein. They demonstrated that this factor is directly involved in the establishment of maternal-foetal circulation and most likely in the development of preeclampsia and intrauterine growth restriction. Indeed, they measured high levels of EG-VEGF in the blood of women with these two diseases during their third trimester of pregnancy.
Sustained high levels of EG-VEGF beyond the first trimester, when it should decrease, would therefore be associated with the onset of these diseases. To test this hypothesis, the biologists used a pregnant mouse model in which they implanted mini-pumps delivering this placental factor from 11.5 days after conception (equivalent to the end of the first trimester of pregnancy in women). Their results show that sustained EG-VEGF levels cause significant anomalies in placental organization and function, including increased placental hypoxia and decreased establishment of maternal-foetal circulation. In addition, the implanted animals showed a significant increase in circulating levels of two factors known to be abnormally high in women with preeclampsia: s-flt1 and endoglin. The animals that continued to receive EG-VEGF beyond the first trimester also developed gestational hypertension, associated with altered renal function unobserved in treated males.
Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension. This factor could therefore serve as a biomarker predicting the onset of preeclampsia.