title: Developmental regulation of the expression of 72 and 92 kd type IV collagenases in human trophoblasts: a possible mechanism for control of trophoblast invasion.
abstract: OBJECTIVE
  During early pregnancy fetal cytotrophoblast cells invade the uterus and penetrate the basement membrane, a property that is characteristic of malignant cells. However, unlike tumor invasion, trophoblast invasion of the uterus is under strict control. This control limits invasion, so that it primarily remains confined to the endometrial aspect of the myometrium and continues only until midgestation. The invasive properties of the trophoblast cells are made possible by the activity of proteolytic enzymes that belong to the metalloproteinases and serine proteinases. Type IV collagenase (metalloproteinase) is considered crucial in the extracellular matrix remodeling that takes place during the invasion process. In this study we set out to characterize the invasive properties of trophoblast cells at different stages of pregnancy.
  
  
  METHODS
  Human trophoblast cells were isolated from first- and third-trimester placentas by trypsin digestion and Percoll fractionation and were then cultured under serum-free conditions. The invasive ability of trophoblast cells was determined by the in vitro invasion assay, in which the ability of cells to penetrate an artificial basement membrane was examined. Metalloproteinase activity was measured by zymography, and the expression of messenger ribonucleic acid transcripts of 72 and 92 kd type IV collagenases was examined by reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  First-trimester trophoblasts were 3.5 time more invasive in vitro than were third-trimester trophoblast cells (p < 0.005). Although first-trimester trophoblasts secreted both species of type IV collagenase, 72 and 92 kd, in large amounts, third-trimester cells secreted the 92 kd and only minimal amounts of 72 kd type IV collagenase. Moreover, first-trimester trophoblasts secreted significantly more (p < 0.05) 92 kd type IV collagenase than did third-trimester trophoblast. The messenger ribonucleic acid transcript expression of 72 and 92 kd type IV collagenases correlated with the activity of these enzymes secreted by first- and third-trimester trophoblasts.
  
  
  CONCLUSIONS
  The described high in situ invasive capacity of first-trimester trophoblast might be explained by the increased expression and production of 72 kd type IV collagenase and the higher expression of 92 kd type IV collagenase by first-trimester trophoblast cells.
authors.affiliation: Department of Obstetrics and Gynecology, Hadassah University, Jerusalem, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Shimonovitz
authors.forename: A
authors.initials: A
authors.lastname: Hurwitz
authors.forename: M
authors.initials: M
authors.lastname: Dushnik
authors.forename: E
authors.initials: E
authors.lastname: Anteby
authors.forename: T
authors.initials: T
authors.lastname: Geva-Eldar
authors.forename: S
authors.initials: S
authors.lastname: Yagel
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020780:Matrix Metalloproteinase 9; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D014327:Trophoblasts / Q000201:enzymology / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase; D017364:Collagenases; D020780:Matrix Metalloproteinase 9