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Am J Reprod Immunol. 2013 Feb;69(2):105-23. doi: 10.1111/aji.12046. Epub 2012 Dec 24.

Endoglin in amniotic fluid as a risk factor for the subsequent development of bronchopulmonary dysplasia.

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1
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD and Detroit, MI 48201, USA.

Abstract

OBJECTIVE:

Cross-talk between inflammation and angiogenesis pathways has been recently reported. The objectives of this study were to: (i) examine whether amniotic fluid (AF) concentrations of soluble endoglin (sEng), a protein with anti-angiogenic properties, change during pregnancy, parturition, or intra-amniotic infection and/or inflammation (IAI); (ii) determine whether an increase in sEng in the AF of patients with preterm labor (PTL) and preterm prelabor rupture of membranes (PROM) is associated with adverse neonatal outcomes; and (iii) investigate potential sources of sEng in AF.

STUDY DESIGN:

A cross-sectional study was conducted to include patients in the following groups: (i) mid-trimester (n = 20); (ii) PTL with term delivery (n = 95); (iii) PTL leading to preterm delivery with (n = 40) and without IAI (n = 46); (iv) preterm PROM with (n = 37) and without IAI (n = 37); (v) term in labor (n = 48) and not in labor (n = 44). AF concentrations of sEng were determined by enzyme-linked immunosorbent assay. Chorioamniotic membranes, umbilical cord blood, and AF macrophages were examined for the expression of endoglin.

RESULTS:

(i) Patients with IAI had a higher median AF concentration of sEng than those without IAI (P = 0.02 for PTL and 0.06 for preterm PROM); (ii) AF concentrations of sEng in the 3rd and 4th quartiles were associated with IAI (OR 2.5 and 7.9, respectively); (iii) an AF sEng concentration ≥779.5 pg/mL was associated with bronchopulmonary dysplasia (BPD) (OR 7.9); (iv) endoglin was co-localized with CD14+ macrophages in AF pellets of patients with IAI by immunofluorescence and flow cytometry; and (v) the concentration of sEng in the supernatant was significantly increased after the treatment of macrophages with endotoxin or TNF-α.

CONCLUSIONS:

Soluble endoglin participates in the host response against IAI. Activated macrophages may be a source of sEng concentrations in the AF of patients with IAI. An increase of sEng in the AF is associated with BPD and adverse neonatal outcomes.

PMID:
23279628
PMCID:
PMC4151572
DOI:
10.1111/aji.12046
[Indexed for MEDLINE]
Free PMC Article
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