OBJECTIVE:
    On a clinical level the etiologies associated with premature rupture of the membranes and preterm labor are virtually identical though these conditions end in distinctly different events. This study was designed to determine differences between preterm labor (PTL) and preterm premature rupture of the membranes (pPROM) using molecular markers of extracellular matrix degradation and apoptosis.

MATERIALS AND METHODS:
    Amniochorion and amniotic fluid (AF) samples collected from gestational age matched groups of women undergoing C-section before term. Samples were collected from two groups of women 1) women with premature rupture of membranes 2) women with PTL with no rupture of membranes. Changes in the expression pattern of mRNA for MMPs, TIMPs, Pro-apoptotic (p53 and Bax) and antiapoptotic (Bcl-2) proteins were quantitated by quantitative PCR. ELISA was used to determine the levels of these proteins in the AF. Multiplex PCR was performed to study the expression of Fas-Fas ligand associated pro-apoptotic genes. Unpaired nonparametric, two-tail Mann-Whitney U, was used to determine statistical significance of QPCR and ELISA. (p<0.05 was considered significant).

RESULTS:
    QPCR results demonstrated an increased mRNA expression for MMP2, MMP9, MT1-MMP and a decreased TIMP2 expression in PROM compared to PTL membranes. ELISA documented an increase in the AF concentration of immunoreactive and bioactive MMP2, MMP9 and immunoreactive levels of MMP3 and a decreased TIMP2 concentration in fluids obtained from PROM compared to PTL groups. The pro-apoptotic genes, p53 and bax were upregulated in PROM when compared to PTL. Antiapoptotic gene (Bcl-2) expression was increased in PTL compared to membranes from PROM. IL-18 (a proapoptotic cytokine) was increased in the AF during PROM compared to PTL. PROM membranes also demonstrated fragmented DNA, expression of FAS and caspase 8 (apoptosis initiator) which were all absent in PTL membranes.

CONCLUSION:
    We have begun to delineate two divergent molecular pathways for premature rupture of membranes and preterm labor. Most likely this is the beginning of the differences that will become evident using molecular biology.