MATRIX METALLOPROTEINASE-2 AND METALLOPROTEINASE-9, AND TISSUE INHIBITOR OF METALLOPROTEINASES-1 OF THE SHEEP PLACENTA DURING THE LAST 1 3 OF GESTATION/

Uteroplacental and fetoplacental blood flows increase dramatically dur ing the last third of gestation. Therefore, angiogenesis and tissue re modelling may regulate placental growth. On days 110, 120, 130, and 14 2 (term=145+/-3; n=5 ewes/day) of gestation, sheep placentae were sepa rated into maternal (caruncular and intercaruncular) and fetal (cotyle donary and intercotyledonary) components; tissues were minced and cult ured (24 h) and media were analysed for gelatinase activity and for ti ssue inhibitor of metalloproteinases-1 (TIMP-1) protein. Both the 72-k Da (matrix metalloproteinase-2; MMP-2) and 95-kDa (matrix metalloprote inase-9; MMP-9) gelatinases were detected by zymography. There was mor e (P<0.001) MMP-2 activity in the caruncle versus intercaruncle and in tercotyledon, and all had greater MMP-2 activity (P<0.001) than the co tyledon. There was less (P<0.04) MMP-9 in the inrercotyledon than in t he other components. By Western analysis, there was more (P<0.004) TIM P-1 (30 kDa) in the caruncle-conditioned media compared to the other t issues, which did not differ from each other (P greater than or equal to 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 int erface of the placentome (trophoblast and binucleate cells), and the e ndothelial cells of microvessels. Therefore, MMP-2, MMP-9, and TIMP-1 are present in the last third of gestation, suggesting that there is a n ongoing tight regulation of tissue remodelling and growth throughout this critical time of pregnancy. (C) 1998 W. B. Saunders Company Ltd.