Abstract
BackgroundPlatelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators. The aim of this study was to test whether platelet-activating factor and lipopolysaccharide were able to induce nitric oxide synthase expression and stimulate the production of nitric oxide in human fetal membrane explants in culture.MethodsFetal membranes were collected from Caesarean sections at term. RNA was extracted from membranes and subjected to a qualitative RT-PCR to assess the baseline expression of iNOS. Discs of fetal membranes were cultured for 24 hours in the presence of platelet-activating factor at a dose range of 0.1 nanomolar – 1 micomolar or 1 microgram/ml lipopolysaccharide. Nitric oxide production was measured via nitrite ions in the culture medium and mRNA for iNOS was detected by RT-PCR.ResultsCulturing the membrane discs in medium containing serum induced nitric oxide synthase expression and platelet-activating factor significantly stimulated the production of nitric oxide under these conditions. When cultured without serum inducible nitric oxide synthase expression was induced by lipopolysaccharide, but not by platelet-activating factor.ConclusionPlatelet-activating factor may have a role in the initiation of labour, at term or preterm, via the increased local production of nitric oxide as an inflammatory mediator. In this model of intrauterine infection, lipopolysaccharide was found to induce iNOS expression by fetal membranes, and this mechanism could be involved in preterm labour.
Highlights
Platelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators
Very low levels of inducible nitric oxide synthase (iNOS) mRNA were found in all membrane samples by nested reverse transcriptionpolymerase chain reaction (RT-PCR) (Figure 2)
This study found that culturing in the presence of serum induced iNOS expression, which confirmed previous findings that culturing with serum can non- induce the expression of enzymes, such as cyclooxygenase-2 [34]
Summary
Platelet-activating factor and nitric oxide may be involved in the initiation of human labour as inflammatory mediators. There is growing evidence for an inflammatory mechanism in the onset of labour at term [8] and preterm [9,10], where inflammatory mediators such as PAF and nitric oxide (NO) may be involved. It has been thought for some time that PAF could be involved with the onset of parturition [11,12], as PAF is associated with fetal lung maturation and is produced by type II pneumocytes, along with surfactant [12,13]. Nitric oxide has been found to be a mediator of cervical ripening, via an inflammatory mechanism [24], suggesting a role in promoting parturition
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