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.
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.


METHODS
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 alpha-defensin-1, beta-defensin-1, calgranulin B and granulysin in the fetal membranes was determined by qRT-PCR.


RESULTS
(1) The expression of alpha-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 alpha-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 beta-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 alpha-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 alpha-defensin-1 mRNA expression in the fetal membranes in patients with PTL and intact membranes and those with PPROM.
Erez
Offer
O
Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, Michigan, USA.
Romero
Roberto
R
Tarca
Adi L
AL
Chaiworapongsa
Tinnakorn
T
Kim
Yeon Mee
YM
Than
Nandor Gabor
NG
Vaisbuch
Edi
E
Draghici
Sorin
S
Tromp
Gerard
G
D000293:Adolescent; D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism; D023082:Defensins / Q000235:genetics / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D007752:Obstetric Labor, Premature / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D055815:Young Adult
D000945:Antigens, Differentiation, T-Lymphocyte; D023181:Antimicrobial Cationic Peptides; D040502:Calgranulin B; D023082:Defensins; C075005:GNLY protein, human; D012333:RNA, Messenger