Introduction Placental activation of Innate Immune system (IIS) is thought to be one of the mechanisms involved in the pathophysiology of preterm labor (PTL). The aim of our study was to evaluate Toll-like receptors (TLRs) 2-3-4 expression in term and preterm placentas. Methods We recruited 37 patients who delivered at our obstetric department. 14 (group A) had a preterm delivery (mean g.a. 25+5 wks). 23 uncomplicated pregnancies (group B) at term (mean g.a. 39+2 wks) were used as controls. We investigated TLRs 2-3-4 expression using immunohistochemical methods in amnios, chorion and deciduas.The pathologist was blind to the clinical results. Results Increased TLR4 expression in amnios (P = 0.0417) and chorion (P = 0.0402) in group A compared to amnios and chorion samples of group B patients. No differences in TLR4 decidual expression (P = 0.8141) between cases and controls. No increased expression of both TLR2 and TLR3 either in cases and in controls at any level (deciduas, amnios and chorion). Moreover we found histological chorionamnionitis in 9 cases on the 14 of group A with histological methods, while in group B the placentas showed no signs of infection. Discussion We hypothesize a model in 3 stages for the pathogenesis of infective PTL. We can consider as a “root cause” the IIS activation by organisms normally present in the endometrial cavity that don’t elicit a proinÀ ammatory response during pregnancy unless the conceptus recognizes them using pattern recognition receptors. We observed an increased TLR4 expression on fetal membranes and not on maternal deciduas.This may suggest that the Gram-organisms that caused TLR4 increased expression at the fetal level and therefore the activation of the cytokine cascade, “¿ nal cause”of PTL, weren’t able to determine the same TLR4 up-regulation at the maternal level, probably because the microbial-host interaction in the deciduas is a symbiotic one. We considered the “fetal genetic predisposition” to the activation of the cytokine cascade as intermediate stage in the pathophysiology of infective PTL. Conclusions Although the number of patients is limited and we still have to con¿ rm our results with quantitative methods however the study suggests that in case of infective PTL, IIS is probably activated at a fetal and not at a maternal level.

Premature Labor and TLR4: Why the Fetus Is Responding and the Mother Isn’t?

Antonio Ragusa;
2012-01-01

Abstract

Introduction Placental activation of Innate Immune system (IIS) is thought to be one of the mechanisms involved in the pathophysiology of preterm labor (PTL). The aim of our study was to evaluate Toll-like receptors (TLRs) 2-3-4 expression in term and preterm placentas. Methods We recruited 37 patients who delivered at our obstetric department. 14 (group A) had a preterm delivery (mean g.a. 25+5 wks). 23 uncomplicated pregnancies (group B) at term (mean g.a. 39+2 wks) were used as controls. We investigated TLRs 2-3-4 expression using immunohistochemical methods in amnios, chorion and deciduas.The pathologist was blind to the clinical results. Results Increased TLR4 expression in amnios (P = 0.0417) and chorion (P = 0.0402) in group A compared to amnios and chorion samples of group B patients. No differences in TLR4 decidual expression (P = 0.8141) between cases and controls. No increased expression of both TLR2 and TLR3 either in cases and in controls at any level (deciduas, amnios and chorion). Moreover we found histological chorionamnionitis in 9 cases on the 14 of group A with histological methods, while in group B the placentas showed no signs of infection. Discussion We hypothesize a model in 3 stages for the pathogenesis of infective PTL. We can consider as a “root cause” the IIS activation by organisms normally present in the endometrial cavity that don’t elicit a proinÀ ammatory response during pregnancy unless the conceptus recognizes them using pattern recognition receptors. We observed an increased TLR4 expression on fetal membranes and not on maternal deciduas.This may suggest that the Gram-organisms that caused TLR4 increased expression at the fetal level and therefore the activation of the cytokine cascade, “¿ nal cause”of PTL, weren’t able to determine the same TLR4 up-regulation at the maternal level, probably because the microbial-host interaction in the deciduas is a symbiotic one. We considered the “fetal genetic predisposition” to the activation of the cytokine cascade as intermediate stage in the pathophysiology of infective PTL. Conclusions Although the number of patients is limited and we still have to con¿ rm our results with quantitative methods however the study suggests that in case of infective PTL, IIS is probably activated at a fetal and not at a maternal level.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/69104
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