Distinct molecular events suggest different pathways for preterm labor andpremature rupture of membranes

OBJECTIVE: On a clinical level, the etiologies associated with premature ru pture of the membranes and preterm labor are virtually identical, though th ese conditions end in distinctly different events. This study was designed to determine differences between preterm labor and preterm premature ruptur e of membranes by using molecular markers of extracellular matrix degradati on and apoptosis. STUDY DESIGN: Amniochorion and amniotic fluid samples were collected from g estational age-matched groups of women undergoing cesarean delivery before term. Samples were collected from 2 groups of women, women with premature r upture of membranes and women with preterm labor with no rupture of membran es. Changes in the expression pattern of messenger ribonucleic acid for mat rix metalloproteinases (MMP), tissue inhibitor of metalloproteinases (TIMP) , and pro-apoptotic (p53 and Bar) and anti-apoptotic (Bcl-2) proteins were identified by quantitative polymerase chain reaction. Enzyme-linked immunos orbent assay was used to determine the levels of these proteins in the amni otic fluid. Multiplex polymerase chain reaction was performed to study the expression of Pas-Pas ligand-associated pro-apoptotic genes. Unpaired nonpa rametric, 2-tailed Mann-Whitney U test was used to determine statistical si gnificance of quantitative polymerase chain reaction and enzyme-linked immu nosorbent assay (P < .05 was considered significant). RESULTS: Quantitative polymerase chain reaction results demonstrated an inc reased mRNA expression for MMP2, MMP9, and MT1-MMP and a decreased expressi on for TIMP2 in prematurely ruptured membranes compared with preterm labor membranes. Enzyme-linked immunosorbent assay documented increases in the am niotic fluid concentrations of immunoreactive and bioactive MMP2 and MMP9 a nd immunoreactive MMP3 and a decreased TIMP2 concentration in fluids obtain ed from the premature rupture of membranes group compared with the preterm labor group. The pro-apoptotic genes p53 and bar were up-regulated in prema ture rupture of membranes when compared with preterm labor. Anti-apoptotic gene (Bcl-2) expression was increased in preterm labor membranes compared w ith prematurely ruptured membranes. Interleukin-18 (a pro-apoptotic cytokin e) was increased in the amniotic fluid during premature rupture of membrane s compared with preterm labor. Prematurely ruptured membranes also demonstr ated fragmented deoxyribonucleic acid and expression of Fas and caspase 8 ( apoptosis initiator), which were all absent in preterm labor membranes. CONCLUSIONS: We have begun to delineate 2 divergent molecular pathways for premature rupture of membranes and preterm labor. Most likely, this is the beginning of the identification of differences that will become evident wit h the use of molecular biology.