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Citations to this article

Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?
Y Zhou, … , M Wheelock, C H Damsky
Y Zhou, … , M Wheelock, C H Damsky
Published May 1, 1997
Citation Information: J Clin Invest. 1997;99(9):2139-2151. https://doi.org/10.1172/JCI119387.
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Research Article Article has an altmetric score of 15

Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion?

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Abstract

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.

Authors

Y Zhou, S J Fisher, M Janatpour, O Genbacev, E Dejana, M Wheelock, C H Damsky

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1995 1994 1991 Total
Citations: 3 7 11 14 15 24 22 22 29 23 26 28 36 20 25 24 30 35 31 34 35 32 34 24 23 30 23 16 4 1 1 1 683
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Citations to this article in year 2013 (36)

Title and authors Publication Year
Culturing cytotrophoblasts reverses gene dysregulation in preeclampsia revealing possible causes
Yan Zhou, Matthew Gormley, Nathan Hunkapiller, Mirhan Kapidzic, Yana Stolyarov, Victoria Feng, Masakazu Nishida, Penelope Drake, Katherine Bianco-Sylvester, Fei Wang, Michael McMaster, Susan Fisher
Journal of Clinical Investigation 2013
Preeclampsia: a link between trophoblast dysregulation and an anti-angiogenic state
ROBERTO ROMERO
Journal of Clinical Investigation 2013
Impaired autophagy by soluble endoglin, under physiological hypoxia in early pregnant period, is involved in poor placentation in preeclampsia
A Nakashima, M Yamanaka-Tatematsu, N Fujita, K Koizumi, T Shima, T Yoshida, T Nikaido, A Okamoto, T Yoshimori, S Saito
Autophagy 2013
Pathophysiology of hypertension in pre-eclampsia: a lesson in integrative physiology
AC Palei, FT Spradley, JP Warrington, EM George, JP Granger
Acta Physiologica 2013
Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction
V Plaks, J Rinkenberger, J Dai, M Flannery, M Sund, K Kanasaki, W Ni, R Kalluri, Z Werb
Proceedings of the National Academy of Sciences 2013
Endoglin: a critical mediator of cardiovascular health
NK Kapur, KJ Morine, M Letarte
Vascular Health and Risk Management 2013
Human placental microRNAs and preeclampsia
D Chen, W Wang
Biology of reproduction 2013
Trophoblasts, invasion, and microRNA
L Doridot, F Miralles, S Barbaux, D Vaiman
Frontiers in Genetics 2013
Decidual cell regulation of natural killer cell-recruiting chemokines: implications for the pathogenesis and prediction of preeclampsia
CJ Lockwood, SJ Huang, CP Chen, Y Huang, J Xu, S Faramarzi, O Kayisli, U Kayisli, L Koopman, D Smedts, LF Buchwalder, F Schatz
The American Journal of Pathology 2013
DNA methyltransferases and TETs in the regulation of differentiation and invasiveness of extra-villous trophoblasts
PC Logan, MD Mitchell, PE Lobie
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
If we know so much about preeclampsia, why haven’t we cured the disease?
JM Roberts, MJ Bell
Journal of Reproductive Immunology 2013
Seldin and Giebisch's The Kidney
CJ Cooper, LD Dworkin, WL Henrich
Seldin and Giebisch's The Kidney 2013
Control of extravillous trophoblast function by the eotaxins CCL11, CCL24 and CCL26
SE Chau, P Murthi, MH Wong, GS Whitley, SP Brennecke, RJ Keogh
Human Reproduction 2013
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
The tumor suppressor gastrokine-1 is expressed in placenta and contributes to the regulation of trophoblast migration
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
Histopathologies, immunolocalization, and a glycan binding screen provide insights into Plasmodium falciparum interactions with the human placenta
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
Placenta 2013
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
Pathologie
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
Physiological genomics 2013
Human Trophoblast Progenitors: Where Do They Reside?
O Genbacev, J Lamb, A Prakobphol, M Donne, M McMaster, S Fisher
Seminars in reproductive medicine 2013

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