240. Decidual inflammation in normal and preeclamptic pregnancies

Abstract

Introduction Preeclampsia is characterized by reduced trophoblast invasion in the uterine wall decidua, harmful placental inflammation, and elevated systemic inflammation and sFlt-1 levels. Danger sensors like toll-like receptor (TLR)2, TLR4 and the nod-like receptor protein (NLRP)3 inflammasome initiate inflammation. These sensors have been associated with placental inflammation in preeclampsia, and maternal cholesterol and uric acid levels represent relevant activators. We have previously shown that trophoblasts have potent inflammatory properties, but it has not been determined how these sensors affects their communication with maternal immune cells in the decidua. Objectives We aimed to investigate cell specific inflammation through TLR2, TLR4 and NLRP3 in decidual trophoblasts and maternal immune cells, and assess the contribution to the harmful placental inflammation in preeclampsia. Methods Decidual biopsies obtained from 44 normal and 48 preeclamptic pregnancies during cesarean sections were analyzed by immunohistochemistry for cell markers and TLR2, TLR4, NLRP3 and IL1-β expression. Automated protein quantification was done in MATLAB. Decidual explants and trophoblasts were primed and stimulated with cholesterol crystals in vitro. IL-1β response was quantified by ELISA. Serum total cholesterol, uric acid, sFlt-1 and C-reactive protein (CRP) were measured by enzymatic assays or ELISA. Results TLR4, NLRP3 and IL1-β were markedly expressed by both trophoblasts and maternal immune cells in the decidua, while TLR2 was mainly expressed by maternal immune cells. Cholesterol crystals induced IL-1β in trophoblasts. Serum cholesterol levels were elevated in preeclamptic compared to healthy pregnancies, correlating to concentrations of hsCRP and sFlt-1. Quantification of danger sensor protein expression comparing normal and preeclamptic pregnancies will be presented. Discussion The expression and function of TLR4 and NLRP3 in trophoblasts and maternal immune cells suggests an inflammatory role in intercellular decidual maternal-fetal communication with potential involvement in preeclampsia.