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Updated: May 30, 2026
Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings
Published on: October 25, 2015
Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep
Suhas G Kallapur1, Boris W Kramer, Christine L Knox
1Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA. suhas.kallapur@cchmc.org
Abstract:
The chorioamnionitis associated with preterm delivery is often polymicrobial with ureaplasma being the most common isolate. To evaluate interactions between the different proinflammatory mediators, we hypothesized that ureaplasma exposure would increase fetal responsiveness to LPS. Fetal sheep were given intra-amniotic (IA) injections of media (control) or Ureaplasma parvum serovar 3 either 7 or 70 d before preterm delivery. Another group received an IA injection of Escherichia coli LPS 2 d prior to delivery. To test for interactions, IA U. parvum-exposed animals were challenged with IA LPS and delivered 2 d later. All animals were delivered at 124 ± 1-d gestation (term = 150 d). Compared with the 2-d LPS exposure group, the U. parvum 70 d + LPS group had 1) decreased lung pro- and anti-inflammatory cytokine expression and 2) fewer CD3(+) T lymphocytes, CCL2(+), myeloperoxidase(+), and PU.1(+) cells in the lung. Interestingly, exposure to U. parvum for 7 d did not change responses to a subsequent IA LPS challenge, and exposure to IA U. parvum alone induced mild lung inflammation. Exposure to U. parvum increased pulmonary TGF-β1 expression but did not change mRNA expression of either the receptor TLR4 or some of the downstream mediators in the lung. Monocytes from fetal blood and lung isolated from U. parvum 70 d + LPS but not U. parvum 7 d + LPS animals had decreased in vitro responsiveness to LPS. These results are consistent with the novel finding of downregulation of LPS responses by chronic but not acute fetal exposures to U. parvum. The findings increase our understanding of how chorioamnionitis-exposed preterm infants may respond to lung injury and postnatal nosocomial infections.
Insights
Chronic Ureaplasma parvum exposure in fetal sheep downregulates fetal lung responses to LPS, impacting preterm infant lung injury outcomes. Acute exposure did not alter these responses.
Area of Science:
- Perinatal Medicine
- Immunology
- Microbiology
Background:
- Chorioamnionitis, common in preterm delivery, is often polymicrobial with Ureaplasma as a frequent isolate.
- Understanding interactions between Ureaplasma and inflammatory mediators is crucial for preterm infant health.
Purpose of the Study:
- To investigate if Ureaplasma exposure alters fetal sheep's inflammatory response to lipopolysaccharide (LPS).
- To determine the impact of acute versus chronic Ureaplasma exposure on fetal lung inflammation and immune cell response.
Main Methods:
- Fetal sheep received intra-amniotic injections of Ureaplasma parvum or media, followed by Escherichia coli LPS challenge at different time points.
- Lung tissue and blood monocytes were analyzed for inflammatory cytokine expression, immune cell infiltration, and LPS responsiveness.
Main Results:
- Chronic (70-day) Ureaplasma exposure significantly decreased lung inflammatory cytokine expression and immune cell presence following LPS challenge.
- Acute (7-day) Ureaplasma exposure did not alter fetal lung response to LPS, while Ureaplasma alone caused mild inflammation.
- Monocytes from chronically exposed fetuses showed reduced in vitro responsiveness to LPS.
Conclusions:
- Chronic fetal exposure to Ureaplasma parvum downregulates fetal lung inflammatory responses to LPS, but acute exposure does not.
- These findings offer insights into how chorioamnionitis may affect preterm infants' susceptibility to lung injury and infections.
