Searchable abstracts of presentations at key conferences on reproductive biology and medicine
Reproduction Abstracts (2014) 1 P322 | DOI: 10.1530/repabs.1.P322

WCRB2014 POSTER PRESENTATIONS (1) (335 abstracts)

Inhibition of the TLR4 signalling pathway protects from intrauterine heat-killed Escherichia coli-induced pre-term delivery

Peck Yin Chin , Camilla Dorian , Mark Hutchinson & Sarah Robertson


The University of Adelaide, Adelaide, Australia.


The pathophysiology of preterm labour is poorly understood and the causal factors uncertain, but inflammatory mechanisms are clearly implicated. Escherichia coli contain lipopolysaccharide, a pathogen-associated molecular pattern (PAMP) which binds Toll-like receptor 4 (TLR4) and related TLR-associated receptors to activate inflammation and induce preterm delivery (PTD). This project seeks to investigate whether inhibition of the TLR4 signalling pathway using small molecule inhibitors of TLR4 signalling may prevent the parturition cascade caused by heat-killed E. coli-induced inflammation. The effect of administration of TLR4 inhibitors in preventing heat-killed E. coli-induced PTD was investigated in C57Bl/6 (B6) mice.

Pregnant B6 females were administered intrauterine heat-killed E. coli or PBS, with or without co-administration of TLR4 inhibitor, on gestational day (GD) 16.5 and were either killed 4 h later for RT-PCR analysis on the gestational tissues, or allowed to deliver pups.

Heat-killed E. coli-induced PTD was successfully alleviated using TLR4 inhibitors in B6 mice, preventing fetal loss associated with death in utero and/or early delivery, resulting in on-time birth with normal perinatal characteristics and survival rates in pups. These results indicate that TLR4 is required for the precocious activation of the inflammatory response induced by heat-killed E. coli and implicates TLR4 as a key trigger for infection-associated preterm labour. Early intervention with TLR4 inhibitors can inhibit progression of the LPS-induced inflammatory cascade and prevent preterm birth without adverse perinatal or postnatal consequences in mice. The TLR pathway warrants further investigation as a potential target for new prevention or treatment options in women with infection-associated, threatened PTD.

Volume 1

World Congress of Reproductive Biology 2014

Edinburgh, UK
02 Sep 2014 - 04 Sep 2014

World Congress of Reproductive Biology 

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