title: Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia.
abstract: 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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 94143-0512, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Lim
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Janatpour
authors.forename: M
authors.initials: M
authors.lastname: McMaster
authors.forename: K
authors.initials: K
authors.lastname: Bass
authors.forename: S H
authors.initials: SH
authors.lastname: Chun
authors.forename: S J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D000328:Adult; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D011225:Pre-Eclampsia / Q000473:pathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D016023:Integrins; D012333:RNA, Messenger; D017364:Collagenases; D020780:Matrix Metalloproteinase 9