BACKGROUND: Preeclampsia adversely affects fetal brain angiogenesis, with potential acute and long-term consequences. However, the mechanisms underlying these cerebrovascular alterations remain unclear. We investigated whether TSP-1 (thrombospondin-1), an antiangiogenic glycoprotein, mediates communication between fetoplacental and fetal brain endothelium in preeclampsia. METHODS: Conditioned media from human umbilical vein endothelial cells derived from normal and preeclamptic pregnancies were used to treat human (human cerebral microvascular endothelial cell line) and murine brain endothelial cells. Proteomic analysis of umbilical cord serum identified differentially expressed proteins, and TSP-1 was validated by Western blot. TSP-1 expression was investigated in umbilical endothelial cells (EA.