Maternal-fetal conflict during placental malaria: hypertension, trophoblast sVEGFR1 expression and maternal inflammation

Abstract

The maternal-fetal relationship is hypothesized to be in genetic conflict over nutrient allocation. Fetal mechanisms that elevate maternal blood pressure increase blood flow to the placenta, nourishing the fetus. This relationship becomes pathological during hypertensive diseases in pregnancy, such as preeclampsia. During placental malaria, a third organism, Plasmodium falciparum , occupies the maternal side of the placenta, and maternal inflammation ensues which results in low birth weight. Both placental malaria and preeclampsia are more common during first pregnancies. This dissertation examines the maternal fetal relationship during placental malaria, specifically regarding maternal blood pressure. Chapter 1 is a review of the literature. Chapter 2 presents the epidemiology of placental malaria and hypertension based on data collected from the Mother Offspring Malaria Project in Muheza, Tanzania. Chapter 3 presents data that placental malaria involves vascular endothelial growth factor (VEGF) and its soluble inhibitor sVEGFR1, a preeclampsia biomarker. Chapter 4 characterizes the maternal inflammatory response in placental malaria, and finds correlation with sVEGFR1 expression.In summation these chapters present data that hypertension occurs in first time mothers with chronic placental malaria, and that genetic conflict occurs between mother and fetus during placental malaria, whereby maternal macrophages in the placenta express the proinflammatory mediator VEGF, and the fetal trophoblast expresses its soluble inhibitor sVEGFR1. Because placental inflammation causes poor fetal outcomes, fetal mechanisms that promote sVEGFR1 expression may be under selective pressure in malaria endemic areas, particularly during first pregnancies, and may have influenced the evolution of preeclampsia.