Sc. Riley et al., Involvement of matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases and apoptosis in tissue remodelling in the sheep placenta, J REPR FERT, 118(1), 2000, pp. 19-27
Placental growth and development is crucial for successful pregnancy. The a
im of this study was to characterize the activity and localization of the m
atrix metalloproteinase 2 (MMP-2) and MMP-9, which are capable of degrading
basement membrane collagen (predominantly collagen type IV), and their end
ogenous tissue inhibitor of matrix metalloproteinases (TIMPs), in amniotic
fluid and in the developing ovine placenta. Cell deletion by apoptosis duri
ng placental development was also examined. Zymography with gelatin as subs
trate indicated that MMP-2 (72 kDa gelatinase A; predominantly latent form)
was present in increasing amounts in amniotic fluid from day 70 of gestati
on to labour (days 140-145), and MMP-9 (92 kDa gelatinase B; predominantly
latent form) was detectable from day 125 to labour; there was no increase i
n MMP-2 or -9 in labour. A broad range of TIMPs was detected in amniotic fl
uid; the molecular masses corresponded to TIMP-1, -2 and -3. Immunohistoche
mical techniques localized MMP-2, MMP-9 and TIMP-3 in the sheep placenta, p
redominantly in the trophoblast layer in uninucleate, but not binucleate, c
ells. However, MMP-2 and -9 activated proteins in placental homogenates wer
e low throughout pregnancy. Apoptosis was identified by morphological crite
ria and also by TdT-mediated dUTP nick end labelling. Apoptosis was present
in discrete regions in the placenta, predominantly in trophoblast cells ne
ar the tips and the basal regions of the fetomaternal interdigitations. Dur
ing pregnancy the sheep placenta becomes more complex and the area of the f
etomaternal interface increases. MMP-2 and -9 are likely to be involved in
breaking down basement membranes to allow cell migration during this proces
s. It is suggested that digestion of supporting extracellular matrix may tr
igger apoptosis and in some way increase the branching pattern in the villi
.