Expression and Activity of Toll-Like Receptors 1–9 in the Human Term Placenta and Changes Associated with Labor at Term

Inflammatory processes are involved in the initiation and maintenance of labor, suggesting that Toll-like receptor (TLR) activity within gestation-associated tissues, such as the placenta, might contribute to the process of parturition. Expression of transcripts for TLR1–TLR10 was examined in term (>37 wk of gestation) human placentas collected in the absence of labor (elective caesarean sections; ECS; n = 11) and after the completion of labor (normal vaginal delivery; NVD; n = 12). Placental explants were cultured in the presence of agonists for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9, and cytokine production after 24 h was examined. All placentas expressed transcripts for TLR1–TLR10. Reactivity to all agonists except CpG oligonucleotides was observed, indicating that, other than TLR9, all of the receptors studied yielded functional responses. Placental explants prepared from NVD placentas (n = 17) produced significantly more TNFA in response to lipopolysaccharide (TLR4 agonist) and resiquimod (TLR7/8 agonist) than explants from ECS placentas (n = 17). In contrast, gene expression analysis revealed that only transcripts for TLR2 and TLR5 were significantly elevated in association with labor. The human term placenta expresses a variety of functional TLRs, indicating that this family of receptors has an important role in parturition via as yet undetermined cell types and signaling pathways.