Increased concentration of pro-matrix metalloproteinase 9 in term fetal membranes overlying the cervix before labor: implications for membrane remodeling and rupture.
OBJECTIVE
Regional structural alterations that develop before labor are important in the mechanisms of both physiologic and pathologic membrane rupture, because they are also detected in preterm prelabor rupture of the fetal membranes, the most common cause of preterm birth (as great as 60%). Matrix metalloproteinases are located in the fetal membranes and are the main mediators of extracellular matrix degradation. The objective of this study was to examine whether gelatinases (matrix metalloproteinases 2 and 9) could be involved in the development of these regional structural changes seen at term before labor.


METHODS
Fetal membranes from patients undergoing elective cesarean delivery were regionally sampled from over the cervix (cervical membranes) and midway between this area and the placental edge (midzone). Fetal membranes obtained after spontaneous labor and delivery at term were also regionally sampled. Matrix metalloproteinase 2 and 9 activities were assessed by gelatin zymography, whereas total matrix metalloproteinase 9 protein was determined by enzyme-linked immunosorbent assay.


RESULTS
Zymography only detected activity corresponding to the pro-matrix metalloproteinase 2 (72 kd) and 9 (92 kd) forms in prelabor fetal membranes. Although the levels of pro-matrix metalloproteinase 2 showed no regional differences, the pro-matrix metalloproteinase 9 level was higher in the cervical area than in the midzone (2.5 +/- 0.98 vs 0.76 +/- 0.28 optical density units/20 microg protein; P <.01). The concentration of pro-matrix metalloproteinase 9 protein in the cervical area was also significantly higher than that in the midzone (6.69 +/- 4.8 vs 1.58 +/- 1.14 ng/mg protein; P <.01). After delivery both pro-matrix metalloproteinase 2 and 9 activities were elevated, whereas pro-matrix metalloproteinase 9 protein activity showed no regional difference between the rupture site and midzone (23.47 +/- 4.5 vs 25. 3 +/- 6.2 ng/mg protein). Active bands of matrix metalloproteinases 2 (66 kd) and 9 (83 kd) were also detected after delivery.


CONCLUSIONS
This study suggests that a specific regional induction of pro-matrix metalloproteinase 9 occurs in the cervical area before labor and may play a role in "programming" this area for subsequent rupture after activation during labor.
McLaren
J
J
Preterm Birth Research Group, Department of Obstetrics and Gynaecology, University of Leicester, United Kingdom.
Taylor
D J
DJ
Bell
S C
SC
D000650:Amnion / Q000502:physiology; D002584:Cervix Uteri / Q000502:physiology*; D002585:Cesarean Section; D004586:Electrophoresis; D004797:Enzyme-Linked Immunosorbent Assay; D005321:Extraembryonic Membranes / Q000201:enzymology / Q000502:physiology*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000502:physiology*; D010920:Placenta / Q000502:physiology; D011247:Pregnancy
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9