Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia

Am J Pathol. 1997 Dec;151(6):1809-18.


During human placental development, cytotrophoblast stem cells differentiate and invade the uterus. Simultaneously, the cells modulate their expression of several classes of stage-specific antigens that mark transitions in the differentiation process and play a role in either uterine invasion (integrin cell-extracellular matrix receptors and matrix metalloproteinase-9) or immune interactions (HLA-G). The pregnancy disease pre-eclampsia is associated with shallow cytotrophoblast invasion. Previously we showed, by immunofluorescence localization on placental tissue, that in pre-eclampsia invasive cytotrophoblasts fail to properly modulate their integrin repertoire. This finding suggests possible abnormalities in the differentiation pathway that leads to uterine invasion. Here we used a culture system that supports this differentiation process to compare the differentiative and invasive potential of cytotrophoblasts obtained from control (n = 8, 22 to 38 weeks) and pre-eclamptic (n = 9, 24 to 38 weeks) placentas. In culture, the cells from pre-eclamptic placentas failed to properly modulate alpha1 integrin and matrix metalloproteinase-9 expression at the protein and mRNA levels. Their invasive potential was also greatly reduced. Likewise, the cells failed to up-regulate HLA-G protein and mRNA expression. These results suggest that defective cytotrophoblast differentiation/invasion can have significant consequences to the outcome of human pregnancy (ie, development of pre-eclampsia) and that, by the time delivery becomes necessary, the defect is not reversed by removing the cells from the maternal environment.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blotting, Northern
  • Cell Differentiation
  • Cells, Cultured
  • Collagenases / genetics
  • Collagenases / metabolism
  • Female
  • HLA Antigens / genetics
  • HLA Antigens / metabolism
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Integrins / genetics
  • Integrins / metabolism
  • Matrix Metalloproteinase 9
  • Pre-Eclampsia / pathology*
  • Pregnancy
  • RNA, Messenger / metabolism
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Trophoblasts / metabolism
  • Trophoblasts / pathology*


  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Integrins
  • RNA, Messenger
  • Collagenases
  • Matrix Metalloproteinase 9