Objective
Toll-like receptors (TLRs), discovered to regulate patterning during embryonic development, were subsequently found to play a role in innate immunity. TLRs recognize microbial ligands as well as host products released during tissue damage or “danger signals” (Science 2002;296:301). Engagement of TLR-4 can induce trophoblast cells to produce pro-inflammatory cytokines. Such cytokines may promote trophoblast cell apoptosis, which is increased in preeclampsia. This study was conducted to determine TLR-4 expression patterns in the extravillous trophoblasts (EVT) in the placental bed of women with and without preeclampsia.
Study design
Placental bed biopsies were obtained from patients with: (1) normal pregnancy at term (n = 40); (2) severe preeclampsia (n = 15); and (3) preterm delivery and intact membranes (PTD) with and without histologic chorioamnionitis (n = 15 for each group). The expression pattern of TLR-4 in the EVT was examined by double immunohistochemistry. Image analysis was conducted and non-parametric statistics were employed for analysis.
Results
(1) The median percentage of TLR-4 positive EVT was significantly higher in patients with preeclampsia than in patients with PTD or normal patients at term (PTD: P = .0001; women at term: P < .0001). (2) The median percentage of TLR-4 positive EVT was significantly higher in patients with preeclampsia than in those with PTD with histologic chorioamnionitis (P = .0057). (3) The median percentage of TLR-4 positive EVT in the placental bed was significantly higher in patients with PTL and histologic chorioamnionitis than in those without these conditions (P = .037).
Conclusion
TLR-4 expression is increased in the extravillous trophoblasts in women with preeclampsia. We propose that “danger signals” may increase the expression of TLR-4 by EVT in the placental bed, which might lead to trophoblast apoptosis and defective hemochorional placentation in preeclampsia.
Article Info
Publication History
9
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
