Mechanisms of Placental Dysfunction in Pregnancy Malaria

The molecular mechanisms by which pregnancy malaria affects the outcome of fetal development are unknown. Megalin, which has been well studied in kidney, has high expression in the placenta from early stages to term, and is proposed to be an important factor in extensive maternofetal exchange during development of the fetus. Pregnancy malaria (PM) is characterized by inflammation in placenta and is associated with low birthweight (LBW), stillborn birth, and other pathologies. It is hypothesized that PM disturbs megalin function/expression/distribution in the brush boarder of syncytiotrophoblast which, in turn, may contribute significantly to pathology of LBW. Our studies show that the presence of infected erythrocytes in placenta at the time of delivery negatively affects protein abundance for megalin and Dab2. This is the first report associating the abundance of placental megalin system proteins with the birth weight of newborn babies, and associating PM with changes in megalin system protein abundance.