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
U. Ulug et al., 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, MOL HUM REP, 7(12), 2001, pp. 1187-1193
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.