• Preterm Premature Rupture of Membranes his term deines spontaneous rupture of the fetal membranes before 37 completed weeks and before labor onset (American College of Obstetricians and Gynecologists, 20 16d). Such rupture likely has various causes, but intrauterine infection, oxidative stress-induced DNA damage, and premature cellular senescence are major predisposing events (Dutta, 2016; Gomez, 1997; Mercer, 2003). Associated risk factors include lower socioeconomic status, body mass index < 19.8, nutritional deiciencies, and cigarette smoking. Women with PPROM carry an enhanced risk for recurrence during a subsequent pregnancy (Bloom, 2001). Despite these known risk factors, none is identified in most cases of pre term rupture.
Increased apoptosis or necroptosis of membrane cellular components and greater levels of specific proteases in membranes and amnionic luid are related to PPROM. Most tensile strength of the membranes is provided by the amnionic extracellular matrix and interstitial amnionic collagens that are produced in mesenchymal cells (Casey, 1996). Thus, collagen degradation has been a focus of research. he MMP family is involved with normal tissue remodeling and particularly with collagen degradation. Some members are found in higher concentrations in amnionic luid from pregnancies with PPROM (Maymon, 2000; Park, 2003; Romero, 2002). MMP activity is in part regulated by tissue inhibitors of matrix metalloproteinases-TI\1Ps. Several of these inhibitors are found in lower concentrations in amnionic fluid from women with ruptured membranes. Elevated MMP levels found at a time when protease inhibitor expression declines urther supports that their expression alters amnionic tensile strength.
Studies of amniochorion explants show greater MMP expression following treatment with certain cytokines (Fortunato, 1999a,b, 2002). With membrane rupture, thrombin activity rises, which activates MMPs and prostaglandin synthesis. Studies by Mogami (2013) provide a mechanism b) which bacterial endotoxin or TNF-. elicits release of fetal fibronectin (FN) by amnion epithelial cells. The FN then binds toll-like receptor 4 in the amnion mesenchymal cells to activate signaling cascades. hese result in augmented prostaglandin E (PGEJ synthesis and elevated activity of MJlIPs. Higher prostaglandin levels promote cervical ripening and uterine contractions. Greater MMP concentrations allow collagen breakdown in the fetal membranes resulting in premature rupture.
In pregnancies with PPROM, the amnion exhibits a higher degree of cell death and more apoptosis markers than that in term amnion (Arechavaleta-Velasco, 2002; Fortunato, 2003). In vitro studies indicate that apoptosis is likely regulated by bacterial endotoxin, IL-13, and TNF-.. In addition, oxidative stress initiated by events other than infection can induce DNA damage, premature senescence, and subsequent inflammation and proteolysis that leads to PPROM (Menon, 2014a,b). Last, there are proteins involved in the synthesis of mature crosslinked collagen or matrix proteins that bind collagen and thereby promote tensile strength. These proteins are altered in membranes with premature rupture (Wang, 2006).