We are investigating a role for the Herpes virus, human cytomegalovirus (HCMV) in preeclampsia, a hypertensive disorder of pregnancy, through its modulation of a bioactive lipid, sphingosine 1-phosphate (S1P). We are examining the effects of HCMV on three characteristics of preeclampsia: (1) the importance of the placenta; (2) the increased systemic vascular constriction and hypertension and (3) abnormal uterine artery perfusion. A second area of research is to define the role of S1P in pregnancy-induced events taking place in the uterus. Pregnancy is accompanied by dramatic uterine adaptations to allow for development of a healthy placenta that then provides adequate support for the fetus. Little is known about the role of S1P in these adaptations. We are examining the role of S1P in 1) the immunological adaptations that are essential to prevent rejection of the fetal allograft; 2) implantation with an emphasis on control of trophoblast invasion; and 3) uterine activation just prior to delivery.