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Updated: Dec 16, 2025
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Expression of S100A Alarmins in Cord Blood Monocytes Is Highly Associated With Chorioamnionitis and Fetal
Veronika Golubinskaya1, Henri Puttonen2, Ing-Marie Fyhr2
1Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
Insights
High S100A alarmin expression in cord blood monocytes identifies preterm infants at risk due to chorioamnionitis and fetal inflammatory response. This finding suggests altered monocyte function in these vulnerable newborns.
Area of Science:
- Neonatal immunology
- Molecular biology
- Perinatal medicine
Background:
- Preterm infants with chorioamnionitis and fetal inflammatory response face significant neonatal morbidity.
- S100A alarmins (S100A8, S100A9, S100A12) are linked to myeloid cell inflammatory activation and monocyte modulation.
Purpose of the Study:
- To investigate S100A alarmin expression in cord blood monocytes of term and preterm infants.
- To correlate S100A expression with clinical factors, inflammatory biomarkers, and monocyte gene pathways.
Main Methods:
- Isolated CD14+ monocytes from term (n=10) and preterm (<30 weeks, n=33) infants.
- Performed RNA sequencing, Ingenuity Pathway Analysis, Multiplex ELISA, and mass spectrometry.
- Diagnosed histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) via placental examination.
Main Results:
- Significantly increased S100A8, S100A9, S100A12 gene expression in preterm infants.
- High S100A expression associated with spontaneous delivery, HCA, FIRS, and elevated inflammatory proteins.
- Differential gene expression and pathway analysis revealed 18 common pathways linked to S100A alarmins, FIRS, and HCA.
Conclusions:
- Elevated S100A alarmin expression in cord blood monocytes identifies a high-risk group of preterm infants with chorioamnionitis and fetal inflammatory response.
- S100A alarmin expression impacts monocyte function, suggesting a role in neonatal inflammatory conditions.
- Further research is needed on the connection between monocyte phenotype, inflammation, and S100A expression in other cell types.
Abstract:
Background: Preterm infants exposed to chorioamnionitis and with a fetal inflammatory response are at risk for neonatal morbidity and adverse outcome. Alarmins S100A8, S100A9, and S100A12 are expressed by myeloid cells and have been associated with inflammatory activation and monocyte modulation. Aim: To study S100A alarmin expression in cord blood monocytes from term healthy and preterm infants and relate results to clinical findings, inflammatory biomarkers and alarmin protein levels, as well as pathways identified by differentially regulated monocyte genes. Methods: Cord blood CD14+ monocytes were isolated from healthy term (n = 10) and preterm infants (<30 weeks gestational age, n = 33) by MACS technology. Monocyte RNA was sequenced and gene expression was analyzed by Principal Component Analysis and hierarchical clustering. Pathways were identified by Ingenuity Pathway Analysis. Inflammatory proteins were measured by Multiplex ELISA, and plasma S100A proteins by mass spectrometry. Histological chorioamnionitis (HCA) and fetal inflammatory response syndrome (FIRS) were diagnosed by placenta histological examination. Results: S100A8, S100A9, and S100A12 gene expression was significantly increased and with a wider range in preterm vs. term infants. High S100A8 and S100A9 gene expression (n = 17) within the preterm group was strongly associated with spontaneous onset of delivery, HCA, FIRS and elevated inflammatory proteins in cord blood, while low expression (n = 16) was associated with impaired fetal growth and physician-initiated delivery. S100A8 and S100A9 protein levels were significantly lower in preterm vs. term infants, but within the preterm group high S100A gene expression, spontaneous onset of labor, HCA and FIRS were associated with elevated protein levels. One thousand nine hundred genes were differentially expressed in preterm infants with high vs. low S100A alarmin expression. Analysis of 124 genes differentially expressed in S100A high as well as FIRS and HCA groups identified 18 common pathways and S100A alarmins represented major hubs in network analyses. Conclusion: High expression of S100A alarmins in cord blood monocytes identifies a distinct clinical risk group of preterm infants exposed to chorioamnionitis and with a fetal inflammatory response. Gene and pathway analyses suggest that high S100A alarmin expression also affects monocyte function. The connection with monocyte phenotype and inflammation-stimulated S100A expression in other cell types (e.g., neutrophils) warrants further investigation.
