Thrombin-enhanced matrix metalloproteinase-1 expression: a mechanism linking placental abruption with premature rupture of the membranes.
OBJECTIVE
Given the strong clinical association between the decidual hemorrhage of placental abruption and subsequent preterm premature rupture of the membranes, we assessed the effects of thrombin on the expression of the potent interstitial collagenase, matrix metalloproteinase-1 (MMP-1), in cultured endometrial stromal and decidual cells.


METHODS
Stromal cells derived from predecidualized cycling endometrium and decidual cells from term decidua were cultured in a defined medium containing estradiol, to mimic the hormonal milieu of the non-pregnant proliferative phase, or estradiol plus medroxyprogesterone acetate (MPA), to mimic the hormonal milieu of pregnancy, in the presence and absence of thrombin. Culture media were examined for MMP-1 protein levels and cell lysates were examined for steady-state MMP-1 mRNA levels.


RESULTS
MPA strongly inhibited MMP-1 levels in endometrial stromal and term decidual cells. However, thrombin overcame this suppression, producing MMP-1 levels that were several-fold higher than control levels.


CONCLUSIONS
Extrapolation of thrombin-enhanced MMP-1 expression in cultured endometrial stromal and decidual cells to the in vivo pregnant state provides an explanation for the strong association between placental abruption and preterm membrane rupture.
Rosen
T
T
Department of Obstetrics and Gynecology, New York University School of Medicine, New York 10016, USA.
Schatz
F
F
Kuczynski
E
E
Lam
H
H
Koo
A B
AB
Lockwood
C J
CJ
D000037:Abruptio Placentae / Q000201:enzymology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000201:enzymology*; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
D012333:RNA, Messenger; D013917:Thrombin; D020781:Matrix Metalloproteinase 1