title: Programmed cell death (apoptosis) as a possible pathway to metalloproteinase activation and fetal membrane degradation in premature rupture of membranes.
abstract: OBJECTIVE
  Increased matrix metalloproteinase 2 expression and activity are associated with premature rupture of fetal membranes. A proapoptotic protein produced in response to deoxyribonucleic acid fragmentation, p53, can bind to the matrix metalloproteinase 2 gene promoter and cause increased gene expression. It promotes apoptosis by inducing the expression of the proapoptotic bax gene and inhibiting the antiapoptotic bcl-2 gene. This study was undertaken to investigate the expression pattern of apoptotic elements in pregnancy complications that may cause increased expression of the gene for matrix metalloproteinase 2.
  
  
  METHODS
  Amniochorial membranes were collected from the following groups of women: (1) women with premature rupture of fetal membranes, (2) women with preterm labor and intact membranes, and (3) women with term labor after vaginal delivery. Deoxyribonucleic acid fragmentation was tested with ligation-mediated polymerase chain reaction and the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyribonucleoside triphosphate end-labeling assay. Matrix metalloproteinase 2, p53, bcl-2, and bax gene expression patterns were studied with quantitative competitive polymerase chain reaction. Statistical analysis was performed with the Tukey-Kramer multiple comparison test.
  
  
  RESULTS
  Quantitative competitive polymerase chain reaction documented a 10-fold increase in the expression of the gene for matrix metalloproteinase 2 in premature rupture of fetal membranes with respect to term and preterm labor. This induction coincided with an increase in the expressions of the proapoptotic genes p53 and bax and a drop in the expression of the antiapoptotic gene bcl-2. Ligation-mediated polymerase chain reaction revealed deoxyribonucleic acid fragmentation in specimens from premature rupture of fetal membranes and not in those from preterm labor or labor at term. Histochemical analysis documented fragmented deoxyribonucleic acid in chorionic and amniotic cells.
  
  
  CONCLUSIONS
  This study suggests that apoptosis is associated with premature rupture of fetal membranes. Deoxyribonucleic acid fragmentation, associated with elevations in the levels of the two proapoptotic gene products evaluated (p53 and bax ) and a drop in the level of the antiapoptotic bcl-2, was seen in premature rupture of the fetal membranes. Induction of matrix metalloproteinase 2 may be a function of p53 gene expression increase in premature rupture of fetal membranes.
authors.affiliation: Maternal-Fetal Group and the Perinatal Research Center of The Women's Health Research and Education Foundation, Nashville, TN 37203, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Fortunato
authors.forename: R
authors.initials: R
authors.lastname: Menon
authors.forename: C
authors.initials: C
authors.lastname: Bryant
authors.forename: S J
authors.initials: SJ
authors.lastname: Lombardi
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000502:physiology; D005321:Extraembryonic Membranes / Q000503:physiopathology*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007743:Labor, Obstetric / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D007752:Obstetric Labor, Premature / Q000235:genetics; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D020778:Matrix Metalloproteinase 2