Inflammatory Signalling in Fetal Membranes: Increased Expression Levels of TLR 1 in the Presence of Preterm Histological Chorioamnionitis (original) (raw)
Related papers
Open Journal of Obstetrics and Gynecology, 2014
Expression of Toll-like receptors at the maternal-fetal interface during normal and complicated pregnancies has aroused interest in the last few years. However, despite the importance of TLR-2 and TLR-4, which recognizes most microorganisms presenting in the amniotic cavity infections associated with prematurity, comparison of the expressions of these receptors is rare in the literature. Thus, the purpose of this study was to compare the gene expression between TLR-2 and TLR-4 in amniochorion membranes of pregnant women with preterm delivery in the presence of histologic chorioamnionitis (HCA). Amniochorion membranes were collected from 40 pregnant women with preterm delivery; 20 presented HCA and 20 did not. Fragments of the membranes were submitted to total RNA extraction, followed by cDNA production by reverse transcription. Real time quantitative PCR was used to quantify the gene expression of the TLRs. mRNA concentrations between TLR-2 and TLR-4 were compared using the nonparametric Mann-Whitney test. TLR-2 expression was higher than TLR-4 expression in the presence of HCA. No difference was observed between TLR-2 and TLR-4 expression in membranes in the absence of inflammatory infiltrate. In conclusion, amniochorion membranes express TLR-2 and TLR-4 and higher TLR-2 expression in the presence of histologic chorioamnionitis suggests that microorganisms recognizable by TLR-2 play an important role in the physiopathology of preterm labor.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2013
To determine whether histologic chorioamnionitis is associated with changes in gene expression of TLR-1,-2,-4 and-6, and to describe the localization of these receptors in fetal membranes. Study design: A total of 135 amniochorion membranes with or without histologic chorioamnionitis from preterm or term deliveries were included. Fragments of membranes were submitted to total RNA extraction. RNA was reverse transcribed and the quantification of TLRs expression measured by real time PCR. Results: All amniochorion membranes expressed TLR-1 and TLR-4, whereas 99.1% of membranes expressed TLR-2 and 77.4% expressed TLR-6. TLR-1 and TLR-2 expressions were significantly higher in membranes with histologic chorioamnionitis as compared to membranes without chorioamnionitis in preterm pregnancies (p = 0.003 and p < 0.001, respectively). Among the membranes of term pregnancies there were no differences in the expressions of such receptors regardless of inflammatory status. Regarding TLR-4 and TLR-6 expression, there was no difference among membranes with or without histologic chorioamnionitis, regardless gestational age at delivery. TLR-1, TLR-2, TLR-4 and TLR-6 expressions were observed in amniotic epithelial, chorionic and decidual cells. Conclusion: Amniochorion membranes express TLR-1, TLR-2, TLR-4 and TLR-6 and increased expression of TLR-1 and TLR-2 is related to the presence of histologic chorioamnionitis in preterm pregnancies. This study provides further evidence that amniochorion membranes act as a mechanical barrier to microorganisms and as components of the innate immune system.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2009
Premature rupture of membranes (PROM) is a normal event during labor that occurs prior to labor onset. When it occurs before 37 weeks of gestation, it is referred to as preterm premature rupture of membranes (PPROM) [1]. Multiple epidemiological and clinical factors have been associated with PPROM. These include race, smoking, sexually transmitted diseases [2,3], maternal vitamin C deficiency [4], obstetric complications [1,2,5], maternal lower genital tract infection [6], and infection and inflammation of the amniochorion which play primary or secondary roles in PPROM pathogenesis [7,8]. Intra-amniotic infection activates a host inflammatory response characterized by cytokine production. Interleukin (IL)-1b, IL-6, IL-8 and tumor necrosis factor-a (TNF-a) have been shown to be present in high concentrations in the amniotic fluid [9,10], the chorion, and fetal membranes [11] of pregnant women with intra-amniotic infection and PPROM. According to Menon et al. [11], membranes are a site of inflammatory cytokine production. These cytokines are thought to play an important role because TNF bioavailability, apoptosis in the chorion, and increased metalloproteinase (MMP) activity may lead to PPROM [12,13]. Several studies have described mechanisms through which pro-inflammatory cytokines lead to labor onset. The main effect appears to be through the up-regulation of prostaglandin production by reproductive tissues. In the presence of intrauterine infection, leukocytes that are recruited into gestational membranes increase cytokine production (reviewed by Bowen et al. [14]). The effect of chorioamnionitis in preterm tissues and the presence of pro-inflammatory cytokines in chorioamniotic membranes have been investigated. Laham et al. [15] showed that IL-8 release from amnion, chorioadecidual, and placental explants did not significantly differ in the absence or presence of chorioamnionitis. These findings are consistent with a previous study showing no difference in the pattern of inflammatory cytokine mRNA expression in women with or without clinically evident intrau
Journal of Maternal-Fetal and Neonatal Medicine, 2012
To determine soluble Toll-like receptor (sTLR) 1, sTLR2 and sTLR6 concentrations in amniotic fluid (AF) of women with preterm prelabor rupture of membranes (PPROM) and if there is an association with microbial invasion of the amniotic cavity and histological chorioamnionitis (HCA). Methods: Cross-sectional study was performed. Forty-two women with singleton PPROM pregnancies at a gestational age between 24 + 0 and 36 + 6 weeks were included in the study (twenty-two women with presence of both microbial invasion of the amniotic cavity and HCA, and 20 women without microbial invasion of the amniotic cavity and HCA). Amniocenteses were performed, and the concentrations of sTLRs were determined by sandwich enzyme-linked immunosorbent assays. Results: Women with microbial invasions of the amniotic cavity and HCA (n = 22) had significantly higher median sTLR1, sTLR2 and sTLR6 levels than those without (n = 20). (20.4 ng/ mL vs. 0.44 ng/mL; p < 0.0001, 577.6 ng/mL vs. 60.7 ng/mL; p < 0.0001 and 0.44 ng/mL vs. 0.26 ng/mL; p = 0.02, respectively). Conclusions: Women with microbial invasion of the amniotic cavity and HCA had higher AF sTLR1, 2 and 6 levels.
European cytokine network, 2007
Our aim was to compare maternal serum concentrations of interleukin(IL)-1alpha IL-1beta, IL-6 and IL-8 in pregnancies complicated by preterm labor (PTL), with the levels in healthy controls at comparable gestational age, and to determine if these assays have any value in the prediction of early-onset neonatal infection or histological chorioamnionitis. The study population consisted of 65 women with new-onset PTL, and 31 healthy controls. Maternal serum concentrations of IL-6 (8.40 versus 3.30 pg/mL; p = 0.002) and IL-1beta (2.20 versus 0.50 pg/mL; p = 0.003) were significantly higher in patients with PTL as compared to healthy pregnant women. The IL-1beta concentration (13.60 versus 1.20 pg/mL; p = 0.02) was significantly higher in the serum of mothers whose babies developed early-onset infections, than in mothers of newborns that were healthy. However, its predictive value, and the value of the other cytokines studied, was poor. In addition, IL-1beta levels (28.79 versus 5.19 pg/m...
Bacterial Modulation of Human Fetal Membrane Toll-like Receptor Expression
American Journal of Reproductive Immunology, 2013
Problem-Preterm premature rupture of fetal membranes (pPROM) occurs in 30-40% of spontaneous preterm births (PTB) and is associated with intra-amniotic infection and inflammation. The membranes may sense and respond to microbes via Toll-like receptors (TLRs), however, little is known about their expression and regulation in this tissue. The objective of this study was to evaluate the expression of TLR1-10 in fetal membranes after exposure to pathogens associated with intra-amniotic infection and PTB. Method of study-Normal human term fetal membrane explants were exposed to various bacteria. After 24hrs RNA was extracted and quantitative RT-PCR performed for TLRs 1-10. Results-Treatment of fetal membranes with Mycoplasma hominis increased expression of TLR4, TLR6, and TLR8 mRNA. Ureaplasma parvum upregulated TLR8 mRNA, and Porphyromonas gingivalis significantly increased fetal membrane TLR7 expression. In contrast, treatment with Gram-negative Escherichia. coli (and its cell wall component LPS) downregulated TLR10 mRNA. No effect was detected for Ureaplasma urealyticum, Gardnerella vaginalis, or Group B Streptococcus. Conclusions-These findings demonstrate that different types of bacteria have distinct effects on fetal membrane TLR expression patterns. Moreover, these findings highlight the disparity of fetal membrane responses to infection and thus, suggest heterogeneity in the mechanisms by which infection-associated pregnancy complications, such as pPROM and PTB, arise.