Matrix metalloproteinases-2 and -9, and tissue inhibitor of metalloproteinases-1 of the sheep placenta during the last third of gestation.

Uteroplacental and fetoplacental blood flows increase dramatically during the last third of gestation. Therefore, angiogenesis and tissue remodelling may regulate placental growth. On days 110, 120, 130, and 142 (term= 145+/-3; n=5 ewes/day) of gestation, sheep placentae were separated into maternal (caruncular and intercaruncular) and fetal (cotyledonary and intercotyledonary) components; tissues were minced and cultured (24 h) and media were analysed for gelatinase activity and for tissue inhibitor of metalloproteinases-1 (TIMP-1) protein. Both the 72-kDa (matrix metalloproteinase-2; MMP-2) and 95-kDa (matrix metalloproteinase-9; MMP-9) gelatinases were detected by zymography. There was more (P<0.001) MMP-2 activity in the caruncle versus intercaruncle and intercotyledon, and all had greater MMP-2 activity (P<0.001) than the cotyledon. There was less (P<0.04) MMP-9 in the intercotyledon than in the other components. By Western analysis, there was more (P<0.004) TIMP-1 (30 kDa) in the caruncle-conditioned media compared to the other tissues, which did not differ from each other (P> or =0.38). The immunohistochemical staining for MMP-2, MMP-9, and TIMP-1 determined that staining was associated with the epithelial cells of the intercotyledon, the uterine glands, cells of the fetomaternal interface of the placentome (trophoblast and binucleate cells), and the endothelial cells of microvessels. Therefore, MMP-2, MMP-9, and TIMP-1 are present in the last third of gestation, suggesting that there is an ongoing tight regulation of tissue remodelling and growth throughout this critical time of pregnancy.