Expression of matrix metalloproteinases and their inhibitors at the feto-maternal interface in unruptured ectopic tubal pregnancy

Abstract

To investigate expression of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs) at the feto-maternal interface and non-implantation sites in unruptured tubal pregnancies. Prospective study. Setting. University teaching hospital. Eighteen patients with unruptured tubal pregnancy undergoing salpingectomy. Immunohistochemistry was used to detect MMP-2, -9 and -14, and TIMP-1, -2 and -3 at the feto-maternal interface and non-implantation regions of the Fallopian tube. Serum levels of human chorionic gonadotropin (β-hCG) were determined, and trophoblastic invasion was histologiclly classified as stage I when limited to the tubal mucosa and stage II when extending to the muscular layer. The relation between serum β-hCG concentration with the depth of trophoblastic invasion into the tubal wall and differential expression of MMPs and TIMPs. A significant difference in the β-hCG concentrations was seen between stage I and II invasion. Immunoreactivity for MMP-2, -9 and -14, and TIMP-1, -2 and -3 was primarily localized to cytotrophoblasts. At the implantation sites, the intensity of MMPs increased along the invasive pathway towards the maternal interstitium. The expression of MMP-2, MMP-14 and TIMP-3 was localized to the epithelium and smooth muscle cells of the Fallopian tube, while expression of MMP-9, TIMP-1 and TIMP-2 was weak or absent. Human chorionic gonadotropin correlated positively with invasion stage of trophoblasts. At ectopic implantation sites, the expression of MMPs gradually increased with increasing invasion depth of trophoblasts. TIMP-1 and TIMP-2 were only weakly expressed. The imbalance between expression of MMPs and TIMPs at the ectopic implantation sites may lead to the extensive destructive degradation of the extracellular matrix.