Bacterial modulation of human fetal membrane Toll-like receptor expression

Abstract

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 TLRs 1-10 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 24 hrs, RNA was extracted and quantitative RT-PCR performed for TLRs1-10.

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 lipopolysaccharide) downregulated TLR10 mRNA. No effect was detected for Ureaplasma urealyticum, Gardnerella vaginalis, or Group B Streptococcus.

Conclusion: 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.

Figure 1. Effect of mycoplasmas on fetal membrane TLR Expression

Fetal membrane explants were cultured with and without M. hominis or U. parvum. Bar chart shows TLR1-10 mRNA expression as the least squares mean (LSM) and Standard Error of fold changes relative to the control. Values were graphed using the control (no treatment) value as a baseline.

Figure 2. Effect of Gram-negative bacteria and LPS on fetal membrane TLR Expression

Fetal membrane explants were cultured with and without LPS, E. coli, G. vaginalis or P. gingivalis. Bar charts show fetal membrane TLR1-10 mRNA expression in response to each bacterial treatment as the least squares mean (LSM) and Standard Error of fold changes relative to the control. Values were graphed using the control (no treatment) value as a baseline.

Figure 3. Effect of Gram-positive bacteria on fetal membrane TLR Expression

Fetal membrane explants were cultured with and without Group B Streptococci. Bar charts show fetal membrane TLR1-10 mRNA expression in response to each bacterial treatment as the least squares mean (LSM) and Standard Error of fold changes relative to the control. Values were graphed using the control (no treatment) value as a baseline.