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 matrix 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 hemochorial placentae have often been compared to metastatic cancer cells, and are known to express MT1-MMP at their invasive edge. So far, however, little is known about MT1-MMP expression in the placenta of non-invasive type including the synepitheliochorial placepta of bovidae. As an approach to assess the role played by MT1-MMP in the non-invasive synepitheliochorial placentation, we determined the open reading frame (ORF) base sequence of caprine MT1-MMP (DDBJ/EMBL/ GenBank database: AB010921); this sequence is the first registered MT1-MMP ORF sequence of artyodactyls which develop placentae 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 counterparts, respectively. Availability of the cloned caprine MT1-MMP cDNA allowed us to carry out Northern blot analysis which revealed that in the placentome, the expression levels of MT1-MMP mRNA were very low on Day 35 of gestation (peri-implantation stage), while the levels gradually increased from Day 75 to Day 100. In the interplacentome regions of the placenta and the uterus, the signal levels were higher than those in the placentome, and increased from Day 35 onward, peaking on Day 75. In situ hybridization experiments revealed that the binucleate trophoblast cells reacted with the MT1-MMP cRNA probe throughout the period examined while the uninuclear principal trophoblast cells did so only on Day 100. Of particular interest is the expression 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-MMP expression in the endometrial epithelial cell populations might reflect extensive remodeling during gestation.