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Published on: November 20, 2015
Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances
Verena A Lambermont1, Elke Kuypers1, Jennifer J P Collins1
1Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands.
Insights
Intra-amniotic lipopolysaccharide exposure in fetal lambs can trigger inflammatory responses in the developing lung. However, these responses appear to resolve over time, suggesting the fetus can overcome in utero inflammation.
Area of Science:
- Perinatal medicine
- Fetal immunology
- Pulmonary development
Background:
- Intra-amniotic lipopolysaccharide (LPS) exposure may impact neonatal outcomes by affecting fetal lung and immune development.
- This study investigated whether intra-amniotic LPS exposure leads to persistent fetal pulmonary responses during lung development in utero.
Purpose of the Study:
- To determine the effects of intra-amniotic lipopolysaccharide (LPS) exposure on fetal lung immune responses and development.
- To assess the persistence and resolution of pulmonary inflammation in response to LPS exposure in preterm lambs.
Main Methods:
- Fetal lambs received intra-amniotic LPS at specific gestational ages (118 or 118 and 123 days).
- Lambs were delivered at various gestational ages (125, 133, or 140 days) for analysis.
- Evaluated immune responses, PU.1 expression, Toll-like receptor (TLR) mRNA levels, mast cells, and pulmonary elastin deposition.
Main Results:
- A single LPS dose increased pulmonary inflammatory markers (PU.1, TLR1, monocytes, lymphocytes, TLR2, TLR6) at different gestational ages.
- Repetitive LPS exposure led to transient increases in neutrophils, monocytes, PU.1, and TLR1/TLR2, with decreases in mast cells and elastin.
- By 140 days of gestation, only PU.1 remained elevated after repetitive LPS exposure, indicating partial resolution.
Conclusions:
- The preterm fetal lung exhibits varied responses to single or repeated intra-amniotic LPS exposure.
- The resolution of inflammatory and structural changes near term suggests the fetus can resolve in utero inflammatory stimuli over time.
Background:
Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal outcome by altering fetal lung and immune system development. We hypothesized that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses as the lungs develop in utero.
Methods:
Fetal lambs were exposed to intra-amniotic LPS at 118 or at 118 and 123 d of gestational age (GA) with delivery at 125, 133, or 140 d (term = 147 d). Immune responses, PU.1 expression, Toll-like receptor (TLR)-1,2,4,6 mRNA levels, mast cell levels, and pulmonary elastin deposition were evaluated.
Results:
After a single dose of LPS, pulmonary inflammatory responses were observed with increases of (i) PU.1 and TLR1 at 125 d GA and (ii) monocytes, lymphocytes, TLR2, and TLR6 at 133 d GA. Repetitive LPS exposure resulted in (i) increases of neutrophils, monocytes, PU.1, and TLR1 at 125 d GA; (ii) increases of neutrophils, PU.1, and TLR2 at 133 d GA; and (iii) decreases of mast cells, elastin foci, TLR4, and TLR6 at early gestation. At 140 d GA, only PU.1 was increased after repetitive LPS exposure.
Conclusion:
The preterm fetal lung can respond to a single exposure or repeated exposures from intra-amniotic LPS in multiple ways, but the absence of inflammatory and structural changes in LPS-exposed fetuses delivered near term suggest that the fetus can resolve an inflammatory stimulus in utero with time.
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