Increased concentration of pro-matrix metalloproteinase 9 in term fetal membranes overlying the cervix before labor: Implications for membrane remodeling and rupture

OBJECTIVES: Regional structural alterations that develop before labor are i mportant in the mechanisms of both physiologic and pathologic membrane rupt ure, because they are also detected in preterm prelabor rupture of the feta l membranes, the most common cause of preterm birth (as great as 60%). Matr ix metalloproteinases are located in the fetal membranes and are the main m ediators of extracellular matrix degradation. The objective of this study w as to examine whether gelatinases (matrix metalloproteinases 2 and 9) could be involved in the development of these regional structural changes seen a t term before labor. STUDY DESIGN: Fetal membranes from patients undergoing elective cesarean de livery were regionally sampled from over the cervix (cervical membranes) an d midway between this area and the placental edge (midzone). Fetal membrane s obtained after spontaneous labor and delivery at term were also regionall y sampled. Matrix metalloproteinase 2 and 9 activities were assessed by gel atin zymography, whereas total matrix metalloproteinase 9 protein was deter mined 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 cer vical area than in the midzone (2.5 +/- 0.98 vs 0.76 +/- 0.28 optical densi ty units/20 mu g protein; P < .01). The concentration of pro-matrix metallo proteinase 9 protein in the cervical area was also significantly higher tha n 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 n o regional difference between the rupture site and midzone (23.47 +/- 4.5 v s 25.3 +/- 6.2 ng/mg protein). Active bands of matrix metalloproteinases 2 (66 kd) and 9 (83 kd) were also detected after delivery. CONCLUSION: This study suggests that a specific regional induction of pro-m atrix metalloproteinase 9 occurs in the cervical area before labor and may play a role in "programming" this area for subsequent rupture after activat ion during labor.