Expression of matrix metalloproteinase-2,-9,-14, and tissue inhibitors of metalloproteinase-1,-2,-3 in the endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy

The extracellular matrix proteolytic machinery has long been recognized as one of the most important mechanisms for regulating trophoblast invasion. M atrix metalloproteinases (MMPs) are a group of proteases involved in this p rocess, and their activities are regulated by tissue inhibitors of MMPs (TI MPs). In this study, we collected rhesus monkey uteri on Days 12, 18, and 2 6 of pregnancy and examined the mRNA expression of MMP-2, -9, -14, and TIMP -1, -2, -3, as well as the activities of MMP-2 and -9 by using in situ hybr idization and gelatin zymography, respectively. The results showed that MMP -2 and -9 were expressed earlier than MMP-14 and TIMPs in the pregnant endo metrium. MMP-14 and TIMP-2 mRNAs appeared in perivascular decidual cells ea rlier than MMP-2 mRNA. On Day 26 of pregnancy, placental villi expressed li ttle MMP-2, -14, and TIMP transcripts but abundant MMP-9 mRNA. Furthermore, MMP-2, -9, -14, and TIMP-1, -2, -3 were highly expressed on the fetal-mate rnal border but were absent in the myometrium. TIMP-3 mRNA in the endometri um was specifically localized to some cells lining the outer membrane of se veral groups of arterioles. Combined with the results obtained by gelatin z ymography, we found that active MMP-2 existed in the endometrium throughout these three phases, while MMP-9 showed considerable activities only on Day s 18 and 26 of pregnancy. The data suggest key roles for MMP-2 and -9 in in vasion of trophoblast cells into the endometrium and the development of the placenta and might indicate that these processes are regulated by MMP14 an d TIMP-1, -2, and -3.