The regulation of trophoblast invasion and decidual reaction by matrix metalloproteinase-2, metalloproteinase-7, and metalloproteinase-9 expressions in the rat endometrium.

PURPOSE: We aimed to evaluate how matrix metalloproteinases (MMPs) regulate the trophoblast invasion and placentation. METHODS: Female rats were divided into the estrous cycle and early pregnancy day groups. Obtained uterine tissues and implantation sites were processed for immunofluorescence and real-time PCR examinations. RESULTS: The mRNA expression of MMP-7 was higher than MMP-2 and MMP-9. Immunofluorescence findings confirmed that MMP-2, MMP-7, and MMP-9 were localized in the endometrial stroma, while MMP-7 was high in glandular and lining epithelial cells throughout the entire estrous cycle. However, their immunolocalizations and mRNA expressions were dramatically changed with the early pregnancy days. The MMP-7 reached very strong immunostaining in the giant trophoblast cells (GTCs), and the cytoplasm of mature and differentiating decidual cells, whereas MMP-2 and MMP-9 were mostly seen in the primary decidual zone (PDZ), GTCs, and the endothelium of blood vessels. CONCLUSIONS: All three MMPs seemed likely to be a key mediator of trophoblast invasion into the decidual region as well as angiogenesis during the placentation process. Due to the strong and wide expression of MMP-7 in the mature decidua, it could be suggested that MMP-7 is important for decidual ECM remodeling and it might be used as a new marker of decidual reaction.

Wingless ligands and beta-catenin expression in the rat endometrium: The role of Wnt3 and Wnt7a/beta-catenin pathway at the embryo-uterine interface.

Wnt/beta-catenin signaling may play an essential role in endometrial decidualization, placentation, and the establishment of pregnancy. We investigate here the possible roles, immunolocalizations, and synthesis of the Wnt3, Wnt7a, and beta-catenin proteins in the rat endometrium during the estrous cycle and early postimplantation period. Wnt3 and Wnt7a had a similar localization and dynamic expression relative to the endometrial stages. Wnt7a immunostaining was not limited only to the luminal epithelial cells, but also to strong stainings in the stromal and endothelial cells. Wnt3, Wnt7a, and beta-catenin were highly synthesized and colocalized at the trophoblast-decidual interface; and were more obvious in the primary decidual zone, the GTCs, and the ectoplacental cone. Beta-catenin was strongly localized at the borders of the mature decidual cells; however, Wnt3 and Wnt7a immunolocalizations were decreased in those cells. As such, the immunolocalization of Wnt3, Wnt7a, and beta-catenin shifted with decidualization and placentation. The expression level of Wnt3, Wnt7a, and beta-catenin messenger RNAs increased in early pregnancy, and especially between Days 8.5 and 9.5. The dramatic changes in the expression of Wnt3, Wnt7a, and beta-catenin observed during the early days of pregnancy and the estrous cycle may indicate their roles in decidualization, stromal cell proliferation, and trophoblast invasion.