Thrombin-enhanced matrix metalloproteinase-1 expression: a mechanism linking placental abruption with premature rupture of the membranes

J Matern Fetal Neonatal Med. 2002 Jan;11(1):11-7. doi: 10.1080/jmf.11.1.11.17.

Abstract

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.

Study design: 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.

Conclusion: 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abruptio Placentae / enzymology*
  • Blotting, Northern
  • Cells, Cultured
  • Decidua / metabolism
  • Female
  • Fetal Membranes, Premature Rupture / enzymology*
  • Humans
  • Matrix Metalloproteinase 1 / drug effects*
  • Matrix Metalloproteinase 1 / metabolism*
  • Pregnancy
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Thrombin / pharmacology*

Substances

  • RNA, Messenger
  • Thrombin
  • Matrix Metalloproteinase 1