Molecular Human Reproduction, Vol. 7, No. 12, 1187-1193,
December 2001
© 2001 European Society of Human Reproduction and Embryology
Implantation and pregnancy |
Matrix metalloproteinase (MMP)-2 and MMP-9 and their inhibitor, TIMP-1, in human term decidua and fetal membranes: the effect of prostaglandin F2
and indomethacin
1 Laboratory for Research in Reproductive Sciences, Department of Obstetrics and Gynecology, Ha'Emek Medical Center, Afula and 2 Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
Degradation and breakdown of gestational membranes and the adjacent decidua are essential processes for the advancement of labour. We have assessed the effect of prostaglandin (PG) synthesis on the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitor of metalloproteinases (TIMP-1) in fetal membranes at the edge of the placenta and decidua, by using ex-vivo organ culture of the tissues in the absence or presence of PGF2
(0.1, 1.0 and 10 µg/ml) or a PG synthesis inhibitor, indomethacin (10–4–10–6 mol/l). Conditioned media were assessed for MMP by zymography on gelatin containing sodium dodecyl sulphate–polyacrylamide gels and for TIMP-1 by Western blot analysis. Compared to the membranes, decidua produced significantly more MMP-2 and MMP-9 as well as TIMP-1. PGF2 caused a 2.4- and 1.9-fold increase in the production of MMP-2 and MMP-9 in the decidua, respectively (P < 0.05), and an 11.3-fold increase of the active form of MMP-2 (62 kDa) which could hardly be detected in basal culture conditions (P < 0.01). PGF2 decreased TIMP-1 production by 70% in the decidua. The production of MMP-2 and MMP-9 and TIMP-1 by the amniotic and chorionic membranes was not affected by PGF2. Indomethacin decreased the production of MMP-2 and MMP-9 by 78 and 35% in chorion, and by 70 and 58% in amnion, respectively (P < 0.05), but did not affect production in decidual tissue. Indomethacin increased the production of TIMP-1 in chorion and amnion [by 4.1- and 4.5-fold respectively (P < 0.01)], but had no effect on decidua. Cumulatively, PGF2 increases decidual gelatinolytic activity. Meanwhile the inhibition of PG production by indomethacin reduces total gelatinolytic activity in fetal membranes, possibly accounting for some of its labour-arresting property.
fetal membranes/indomethacin/matrix metalloproteinase/prostaglandin F2/TIMP-1
3 On leave from the Bahceci Women's Health Care Center, Istanbul, Turkey
4 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Ha'Emek Medical Centre, Afula 18101, Israel. E-mail: shalev_e{at}hotmail.com
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