Establishment of the human placenta requires that fetal cytotrophoblast stem cells in anchoring chorionic villi become invasive. These cytotrophoblasts aggregate into cell columns and invade both the uterine interstitium and vasculature, anchoring the fetus to the mother and establishing blood flow to the placenta. Cytotrophoblasts colonizing spiral arterioles replace maternal endothelium as far as the first third of the myometrium. We show here that differentiating cytotrophoblasts transform their adhesion receptor phenotype so as to resemble the endothelial cells they replace. Cytotrophoblasts in cell columns show reduced E-cadherin staining and express VE-(endothelial) cadherin, platelet-endothelial adhesion molecule-1, vascular endothelial adhesion molecule-1, and alpha-4-integrins. Cytotrophoblasts in the uterine interstitium and maternal vasculature continue to express these receptors, and, like endothelial cells during angiogenesis, also stain for alphaVbeta3. In functional studies, alphaVbeta3 and VE-cadherin enhance, while E-cadherin restrains, cytotrophoblast invasiveness. Cytotrophoblasts expressing alpha4 integrins bound immobilized VCAM-1 in vitro, suggesting that this receptor-pair could mediate cytotrophoblast-endothelium or cytotrophoblast-cytotrophoblast interactions in vivo, during endovascular invasion. In the pregnancy disorder preeclampsia, in which endovascular invasion remains superficial, cytotrophoblasts fail to express most of these endothelial markers (Zhou et al., 1997. J. Clin. Invest. 99:2152-2164.), suggesting that this adhesion phenotype switch is required for successful endovascular invasion and normal placentation.
Y Zhou, S J Fisher, M Janatpour, O Genbacev, E Dejana, M Wheelock, C H Damsky
Title and authors | Publication | Year |
---|---|---|
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Journal of Clinical Investigation | 2013 |
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Proceedings of the National Academy of Sciences | 2013 |
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Decidual cell regulation of natural killer cell-recruiting chemokines: implications for the pathogenesis and prediction of preeclampsia
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The American Journal of Pathology | 2013 |
DNA methyltransferases and TETs in the regulation of differentiation and invasiveness of extra-villous trophoblasts
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Frontiers in Genetics | 2013 |
Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling
M Knöfler, J Pollheimer |
Frontiers in Genetics | 2013 |
Handbook of Stem Cells
M Amit, J Itskovitz-Eldor |
Handbook of Stem Cells | 2013 |
Comparison of extravillous trophoblast cells derived from human embryonic stem cells and from first trimester human placentas
BP Telugu, K Adachi, JM Schlitt, T Ezashi, DJ Schust, RM Roberts, LC Schulz |
Placenta | 2013 |
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Seldin and Giebisch's The Kidney
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Seldin and Giebisch's The Kidney | 2013 |
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The effects of magnesium sulfate on placental vascular endothelial growth factor expression in preeclampsia†
AY Weintraub, A Amash, T Eshkoli, EP Haber, B Bronfenmacher, E Sheiner, G Holcberg, M Huleihel |
Hypertension in Pregnancy | 2013 |
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FB Fahlbusch, M Ruebner, H Huebner, G Volkert, C Zuern, F Thiel, M Koch, C Menendez-Castro, DL Wachter, A Hartner, W Rascher |
Placenta | 2013 |
The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast function
MV Sinderen, C Cuman, A Winship, E Menkhorst, E Dimitriadis |
Placenta | 2013 |
BMP10 as a potent inducer of trophoblast differentiation in human embryonic and induced pluripotent stem cells
B Lichtner, P Knaus, H Lehrach, J Adjaye |
Biomaterials | 2013 |
MicroRNAs in Human Placental Development and Pregnancy Complications
G Fu, J Brkić, H Hayder, C Peng |
International journal of molecular sciences | 2013 |
The differential expression of Kiss1, MMP9 and angiogenic regulators across the feto-maternal interface of healthy human pregnancies: implications for trophoblast invasion and vessel development
M Matjila, R Millar, Z der Spuy, A Katz |
PloS one | 2013 |
AT1, AT2, and AT(1-7) receptor expression in the uteroplacental unit of normotensive and hypertensive rats during early and late pregnancy
LM Yamaleyeva, LA Neves, K Coveleskie, DI Diz, PE Gallagher, KB Brosnihan |
Placenta | 2013 |
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BS Hromatka, S Ngeleza, JJ Adibi, RK Niles, AK Tshefu, SJ Fisher |
Biology of reproduction | 2013 |
5-aza-dC treatment induces mesenchymal-to-epithelial transition in 1st trimester trophoblast cell line HTR8/SVneo
Y Chen, K Wang, R Leach |
Biochemical and Biophysical Research Communications | 2013 |
A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development
M Aghababaei, S Perdu, K Irvine, AG Beristain |
Molecular Human Reproduction | 2013 |
Mechanisms and Prevention of Alloimmunization in Pregnancy:
J Kjeldsen-Kragh, B Skogen |
Obstetrical & Gynecological Survey | 2013 |
HLA-G regulates the invasive properties of JEG-3 choriocarcinoma cells by controlling STAT3 activation
X Liu, W Gu, X Li |
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Kisspeptin/KISS1R signaling potentiates extravillous trophoblast adhesion to type-I collagen in a PKC- and ERK1/2-dependent manner: Kisspeptin Potentiates EVT Adhesion
J Taylor, M Pampillo, M Bhattacharya, AV Babwah |
Molecular Reproduction and Development | 2013 |
Biomarkers for the management of pre-eclampsia in pregnant women
LT Petla, R Chikkala, KS Ratnakar, V Kodati, V Sritharan |
The Indian journal of medical research | 2013 |
Transforming Growth Factor- 1 Inhibits Trophoblast Cell Invasion by Inducing Snail-mediated Down-regulation of Vascular Endothelial-cadherin Protein
JC Cheng, HM Chang, PC Leung |
The Journal of biological chemistry | 2013 |
The Differential Expression of Kiss1, MMP9 and Angiogenic Regulators across the Feto-Maternal Interface of Healthy Human Pregnancies: Implications for Trophoblast Invasion and Vessel Development
M Matjila, R Millar, Z der Spuy, A Katz, V Sanchez-Margalet |
PloS one | 2013 |
Human Placental MicroRNAs and Preeclampsia1
D Chen, W Wang |
Biology of reproduction | 2013 |
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M Stolte, J Rüschoff, G Klöppel |
Der Pathologe | 2013 |
Aberrant placenta gene expression pattern in bovine pregnancies established after transfer of cloned or in vitro produced embryos
D Salilew-Wondim, D Tesfaye, M Hossain, E Held, F Rings, E Tholen, C Looft, U Cinar, K Schellander, M Hoelker |
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