Expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) mRNA in trophoblast and endometrial epithelial cell populations of the synepitheliochorial placenta of goats (Capra hircus)

Membrane-type 1 matrix metalloproteinase (MT1-MMP), a membrane-bound matrix metalloproteinase, plays crucial roles in cellular migration through the m atrix during embryogenesis, wound healing, and the invasion of host tissues by cancer cells. Mammalian trophoblast cells exhibit different degrees of invasiveness towards the endometrium in different species during gestation. The highly invasive trophoblast cells of primates and rodents which form h emo-chorial placentae have often been compared to metastatic cancer cells, and are known to express MT1-MMP at their invasive edge. So far, however, l ittle is known about MT1-MMP expression in the placenta of noninvasive type including the synepitheliochorial placenta of bovidae. As an approach to a ssess the role played by MT1-MMP in the non-invasive synepitheliochorial pl acentation, we determined the open reading frame (ORF) base sequence of cap rine MT1-MMP (DDBJ/EMBL/GenBank database: AB010921); this sequence is the f irst registered MT1-MMP ORF sequence of artyodactyls which develop placenta e of the non-invasive type. The deduced amino acid sequence of caprine MT1- MMP exhibited 92, 87 and 89% identity with its human, mouse and rat counter parts, respectively. Availability of the cloned caprine MT1-MMP cDNA allowe d us to carry out Northern blot analysis which revealed that in the placent ome, the expression levels of MT1-MMP mRNA were very low on Day 35 of gesta tion (peri-implantation stage), while the levels gradually increased from D ay 75 to Day 100. In the interplacentome regions of the placenta and the ut erus, the signal levels were higher than those in the placentome, and incre ased from Day 35 onward, peaking on Day 75. In situ hybridization experimen ts revealed that the binucleate trophoblast cells reacted with the MT1-MMP cRNA probe throughout the period examined while the uninuclear principal tr ophoblast cells did so only on Day 100. Of particular interest is the expre ssion of MT1-MMP transcripts in the luminal and glandular epithelial cells of the gestational endometrium, since epithelial cells in general have been noted to lack MMP expression, including MT-MMPs. The high levels of MT1-MM P expression in the endometrial epithelial cell populations might reflect e xtensive remodeling during gestation.