Matrix metalloproteinase (MMP)-2 and MMP-9 and their inhibitor, TIMP-1, inhuman term decidua and fetal membranes: the effect of prostaglandin F-2 alpha and indomethacin

Degradation and breakdown of gestational membranes and the adjacent decidua are essential processes for the advancement of labour. We have assessed th e effect of prostaglandin (PG) synthesis on the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9 and tissue inhibitor of metallop roteinases (TIMP-1) in fetal membranes at the edge of the placenta and deci dua, by using ex-vivo organ culture of the tissues in the absence or presen ce of PGF(2 alpha) (0.1, 1.0 and 10 mug/ml) or a PG synthesis inhibitor, in domethacin (10(-4)-1.0(-6) mol/1). 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, de cidua produced significantly more MMP-2 and MMP-9 as well as TIMP-1. PGF(2 alpha) caused a 2.4- and 1.9-fold increase in the production of MMP-2 and M MP-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 c ulture conditions (P < 0.01). PGF(2 alpha) decreased TIMP-1 production by 7 0% in the decidua. The production of MMP-2 and MMP-9 and TIMP-1 by the amni otic and chorionic membranes was not affected by PGF(2 alpha). 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 produc tion 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 ha d no effect on decidua. Cumulatively, PGF(2 alpha) increases decidual gelat inolytic activity. Meanwhile the inhibition of PG production by indomethaci n reduces total gelatinolytic activity in fetal membranes, possibly account ing for some of its labour-arresting property.