Secretion of matrix metalloproteinase-2, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases into the intrauterine compartments during early pregnancy

Matrix metalloproteinases (MMPs) are important enzymes in tissue remodellin g, a key event for the development of the fetal membranes and placenta and establishing the fete-maternal interface during early pregnancy. This study has examined the secretion of the gelatinases, MMP-2 (72 kDa) and MMP-9 (9 2 kDa), and the endogenous tissue inhibitors of metalloproteinases (TIMPs) into extra-embryonic coelomic and amniotic fluids, the two principal intra- uterine compartments of the first trimester, and compared them to amniotic fluid collected later in gestation. In extra-embryonic coelomic fluid, gela tin zymography demonstrated that MMP-2 (72 kDa) was the predominant gelatin ase, with some MMP-9 present. A broad range of TIMPs corresponding to TIMP- 1 and TIMP-2, glycosylated and unglycosylated TIMP-3 and TIMP-4 was detecte d in this compartment by reverse zymography and immunoblot analyses. There was little gelatinase or TIMP activity in amniotic fluid in the first trime ster. In amniotic fluid from the second trimester after fusion of the membr anes obliterating the extra-embryonic coelom, and at term elective caesarea n section, MMP-2 is the predominant gelatinase present, with a broad spectr um of TIMPs. These findings demonstrate that predominantly MMP-2 and also M MP-9, regulated by a range of TIMPs, are involved in intra-uterine tissue r emodelling during the establishment of pregnancy.