Placental TLR/NLR expression signatures are altered with gestational age and inflammation

Objective: To quantify changes in placental expression of Toll-like receptors (TLRs) and nuclear oligomerization domain (NOD)-like receptors (NLRs) gene with (1) advancing gestational age (GA) and (2) exposure to chorioamnionitis (CA) and preterm premature rupture of membrane (PPROM). Methods: Placental tissue was collected at the time of birth from 83 subjects with live birth pregnancies from 24- to 40-week gestation between 2009 and 2013. Real-time RT-PCR analysis of 13 TLR/NLR genes involved in bacterial sensing was performed using specific probes. Results: Of 83 patients enrolled, 61 were preterm (p = 0.0025) and TLR4 (p = 0.0005) were found to increase progressively with GA. We found significant changes in TLR5 (p = 0.01) with CA, NFKBIA (p = 0.016) with PPROM, NKKBIA (p = 0.003), and NFKB1 (p = 0.009) with CA and PPROM. Conclusion: RIPK2 (mediator of NOD-dependent NF-kB signaling) and TLR4 progressively increased with GA. We speculate this upregulation may be involved in initiating labor and delivery at term. Increase in NFKBIA seen in PPROM and CA might represent a counter regulatory mechanism to decrease inflammation in these conditions. This study provides new information on relationships between GA, CA/PPROM, and TLR/NLR signaling in the placenta.