Decreased Expression of Angiogenic Factors in Placentas with Chorioamnionitis after Preterm Birth

Abstract

Chorioamnionitis and funisitis are associated with neonatal morbidity and mortality. We hypothesized that chorioamnionitis may stress fetal endothelium, activate proinflammatory gene transcription. and affect angiogenic homeostasis in fetal capillaries. Placentas from preterm infants were stained for heat-shock protein 70, nuclear factor-B, hypoxia-inducible factor-1␣, and vascular endothelial growth factor (VEGF). VEGF receptors (VEGF-R) 1 and 2 as well as the receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domains (TIE-2), which is involved in vascular remodeling, were quantified. Immunohistochemistry was analyzed by counting positive capillaries in placental terminal villi. Staining intensity was quantified by a three-step semiquantitative scale. The samples were divided into three matched groups according to histology: chorioamnionitis with funisitis ("funisitis"), chorioamnionitis without funisitis ("chorioamnionitis"), and control group with no inflammation. In tissues from the funisitis or chorioamnionitis group, heat-shock protein 70 expression was increased over the control group. More nuclear factor-B-positive nuclei of endothelial cells in capillaries were counted in the funisitis and chorioamnionitis groups. Expression of VEGF and VEGF-R1 and -R2 were reduced in cases of funisitis or chorioamnionitis in comparison with controls. Hypoxia-inducible factor-1␣ expression tended to be slightly lower in the funisitis and chorioamnionitis groups but did not reach statistical significance. We speculate that cellular stress and changes in angiogenic homeostasis induced by proinflammatory activation of fetal endothelium in chorioamnionitis may not be limited to the placenta but may also involve other fetal organs. (Pediatr Res 58: 607-612, 2005) Abbreviations BPD, bronchopulmonary dysplasia CI, confidence interval HIF-1␣ hypoxia-inducible factor-1␣ HRP, horseradish peroxidase HSP70, heat-shock protein 70 IL, interleukin NF-B, nuclear factor-B TIE-2, tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 VEGF, vascular endothelial growth factor VEGF-R, vascular endothelial growth factor receptor Chorioamnionitis is very common in preterm birth (1). Microbial infection of the amnion and chorion are detected in 60% of all preterm deliveries (2). Funisitis is diagnosed as an infiltration of neutrophils in the umbilical cord vessels (3) and can be considered as a progression of chorioamnionitis with systemic inflammatory response syndrome of the fetus (4). Although fetal inflammation reduces the incidence of respiratory distress syndrome (5,6) and increases the survival of preterm infants (7), the fetal inflammatory response has been associated with increased neonatal morbidity. The mechanisms by which fetal inflammation increases the incidence of bronchopulmonary dysplasia (BPD) (8), retinopathy of prematurity (9), intracranial hemorrhage (10), cerebral palsy, and adverse neurodevelopmental outcome (11-13) are not fully understood. Recently, a new poten...

Chorioamnionitis, respiratory distress syndrome and bronchopulmonary dysplasia in extremely low birth weight infants

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Antenatal inflammation and lung injury: prenatal origin of neonatal disease

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Airway Concentrations of Angiopoietin-1 and Endostatin in Ventilated Extremely Premature Infants Are Decreased After Funisitis and Unbalanced With Bronchopulmonary Dysplasia/Death

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