Differential expression pattern of genes encoding for anti-microbial peptides in the fetal membranes of patients with spontaneous preterm labor and intact membranes and those with preterm prelabor rupture of the membranes

Abstract

Objective. Increased amniotic fluid concentrations of anti-microbial peptides, components of the innate immune system, have been reported in patients with preterm labor (PTL) with intact membranes and intra-amniotic infection and/or inflammation (IAI), as well as in patients with preterm prelabor rupture of the membranes (PPROM). This study was designed to confirm these results using a targeted approach, detecting DEFA1, DEFB1, GNLY, and S100A9 gene expression in the choriamniotic membranes in pregnancies complicated with PTL and intact membranes or PPROM, with and without histologic chorioamnionitis.

Study design. Human fetal membranes were obtained from patients in the following groups: (1) PTL with intact membranes (n = 15); (2) PTL with intact membranes with histologic chorioamnionitis (n = 12); (3) PPROM (n = 17); and (4) PPROM with histologic chorioamnionitis (n = 21). The mRNA expression of α-defensin-1, β-defensin-1, calgranulin B and granulysin in the fetal membranes was determined by qRT-PCR.

Results. (1) The expression of α-defensin-1 mRNA in the fetal membranes was higher in patients with PTL and intact membranes with histologic chorioamnionitis, than those without chorioamnionitis (19.4-fold, p < 0.001); (2) Among patients with histologic chorioamnionitis, patients with PTL and intact membranes had a higher α-defensin-1 mRNA expression than those with PPROM (5.5-fold, p = 0.003); (3) Histologic chorioamnionitis was associated with a higher calgranulin B mRNA expression in the chorioamniotic membranes of patients with both PTL and intact membranes (7.9-fold, p = 0.03) and PPROM (7.6-fold, p < 0.0001); (4) The expression of calgranulin B mRNA in the fetal membranes was higher in patients with PTL and intact membranes without histologic chorioamnionitis than in those with PPROM without histologic chorioamnionitis (2.7-fold, p = 0.03); (5) There were no differences in the expression of β-defensin-1 and granulysin in the chorioamniotic membranes between the study groups even in the presence of histologic chorioamnioniotis.

Conclusions. (1) Among patients with histologic chorioamnionitis, the mRNA expression of α-defensin-1 and calgranulin B in the fetal membranes of patients with PTL and intact membranes as well as that of calgranulin B in the fetal membranes of patients with PPROM is higher than in the membranes of those without histologic chorioamnionitis; (2) histologic chorioamnionitis is associated with differences in the pattern of α-defensin-1 mRNA expression in the fetal membranes in patients with PTL and intact membranes and those with PPROM.

Keywords:

• Human neutrophil peptide
• α-defensin
• β-defensin
• calgranulin
• calprotectin
• granulysin
• preterm prelabour rupture of membranes
• spontaneous preterm delivery

The authors thank Lark Technologies, Inc. (Houston, TX) for performing the qRT-PCR experiments. They wish to acknowledge the invaluable contributions made to this manuscript by Sandy Field, Gerardo Rodriguez, and the nursing staff of the Perinatology Research Branch and the Detroit Medical Center.