Question: 

Intrauterine infection frequently causes prematurity and postnatal life-threatening gastrointestinal dysmotility. We investigated how maternal endotoxemia influences contractility and protein composition of the contractile machinery in murine pubs (E18.5).

Methods: 

Pregnant mice (E17.5) received either LPS or 0.9%NaCl i.p. 12h thereafter, the pubs of the LPS- (LPS), 0.9%NaCl- (NaCl) treated and untreated (controls) mothers were prepared. The fetal ileum was isolated for Western Blot analysis of contractile proteins and tension measurements. Specimens of liver and ileum were processed for histology.

Results: 

Spontaneous breath was impaired in LPS whereupon three degrees of illness were defined. In LPS, liver and ileum were more heavily infiltrated by leukocytes, while microscopically maturation of the ileum was not altered by LPS. The alpha/beta-actin ratio was higher in LPS. Passive stiffness was decreased whereas the very minor spontaneous rhythmic activity of the fetal ileum was not affected by LPS. KCl (45mM) induced a weak tonic contraction in LPS only whereas carbachol induced a slowly tonic contraction after an initial relaxation in all groups. The EC₅₀-values were similar, however, maximal force (0.01mM carbachol) decreased in parallel with disease severity. Forskolin and the guanylate cyclase activator, BAY41-2272 relaxed carbachol-contracted LPS and controls equally but the PDE5-inhibitor sildenafil (0.01mM) relaxed LPS and NaCl significantly more than controls (80% versus 30%).

Conclusion: 

Maternal endotoxemia depresses fetal ileal contractile response to carbachol and increases sensitivity to a PDE5-inhibitor in the fetal ileum. In addition, the ileum exhibits accelerated maturation and, as well as the liver,, shows signs of inflammation.