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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 2015 (26)

Title and authors Publication Year
Pre-eclampsia has an adverse impact on maternal and fetal health
S Lin, D Leonard, MA Co, D Mukhopadhyay, B Giri, L Perger, MR Beeram, TJ Kuehl, MN Uddin
Translational Research 2015
Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3′,5′-cyclic monophosphate signaling
JM Bolnick, BA Kilburn, AD Bolnick, MP Diamond, M Singh, M Hertz, J Dai, DR Armant
Fertility and Sterility 2015
Vascular Endothelial Growth Factor-A (VEGF-A) Mediates Activin A-Induced Human Trophoblast Endothelial-Like Tube Formation
Y Li, H Zhu, C Klausen, B Peng, PC Leung
Endocrinology 2015
Epithelial-mesenchymal transition during extravillous trophoblast differentiation
JE Davies, J Pollheimer, HE Yong, MI Kokkinos, B Kalionis, M Knöfler, P Murthi
Cell adhesion & migration 2015
Differentiation of first trimester cytotrophoblast to extravillous trophoblast involves an epithelial–mesenchymal transition
S DaSilva-Arnold, JL James, A Al-Khan, S Zamudio, NP Illsley
Placenta 2015
Cell Signaling During Mammalian Early Embryo Development
HJ Leese, DR Brison
2015
Cell Signaling During Mammalian Early Embryo Development
HJ Leese, DR Brison
2015
Cell Signaling During Mammalian Early Embryo Development
HJ Leese, DR Brison
2015
Cell Signaling During Mammalian Early Embryo Development
HJ Leese, DR Brison
2015
The physiologic and therapeutic role of heparin in implantation and placentation
M Quaranta, O Erez, SA Mastrolia, A Koifman, E Leron, T Eshkoli, M Mazor, G Holcberg
PeerJ 2015
Collagen type IV at the fetal–maternal interface
CM Oefner, A Sharkey, L Gardner, H Critchley, M Oyen, A Moffett
Placenta 2015
ADAM12-directed ectodomain shedding of E-cadherin potentiates trophoblast fusion
M Aghababaei, K Hogg, S Perdu, WP Robinson, AG Beristain
Cell Death and Differentiation 2015
The role of arginine, homoarginine and nitric oxide in pregnancy
A Khalil, L Hardman, P O´Brien
Amino Acids 2015
Protective effect of (±)α-tocopherol on brominated diphenyl ether-47-stimulated prostaglandin pathways in human extravillous trophoblasts in vitro
HR Park, R Loch-Caruso
Toxicology in Vitro 2015
Chesley's Hypertensive Disorders in Pregnancy
SJ Fisher, M McMaster, JM Roberts
Chesley's Hypertensive Disorders in Pregnancy 2015
Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation
P Kumar, TL Thirkill, J Ji, LH Monte, GC Douglas, R Oshima
PloS one 2015
Benzo(a)pyrene inhibits migration and invasion of extravillous trophoblast HTR-8/SVneo cells via activation of the ERK and JNK pathway: BaP inhibits migration and invasion of extravillous trophoblast HTR-8/SVneo cells
L Liu, Y Wang, C Shen, J He, X Liu, Y Ding, R Gao, X Chen
Journal of Applied Toxicology 2015
The hydatidiform mole
JJ Candelier
Cell adhesion & migration 2015
Laminin α4 (LAMA4) Expression Promotes Trophoblast Cell Invasion, Migration, and Angiogenesis and is Lowered in Pre-Eclamptic Placentas
N Shan, X Zhang, X Xiao, H Zhang, C Tong, X Luo, Y Chen, X Liu, N Yin, Q Deng, H Qi
Placenta 2015
Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion
AR Highet, SM Khoda, S Buckberry, S Leemaqz, T Bianco-Miotto, E Harrington, C Ricciardelli, CT Roberts
European Journal of Cell Biology 2015
Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification
T Zdravkovic, KL Nazor, N Larocque, M Gormley, M Donne, N Hunkapillar, G Giritharan, HS Bernstein, G Wei, M Hebrok, X Zeng, O Genbacev, A Mattis, MT McMaster, A Krtolica, D Valbuena, C Simon, LC Laurent, JF Loring, SJ Fisher
Development (Cambridge, England) 2015
Estradiol Elicits Proapoptotic and Antiproliferative Effects in Human Trophoblast Cells
S Patel, B Kilburn, A Imudia, DR Armant, DF Skafar
Biology of reproduction 2015
Human Placental Trophoblasts: Impact of Maternal Nutrition
T Henriksen, A Holme, H Horne, M Holm, T Michelsen
Human Placental Trophoblasts: Impact of Maternal Nutrition 2015
Effect of Bisphenol A on invasion ability of human trophoblastic cell line BeWo
Zi-Yi Wang, Jing Lu, Yuan-Zhen Zhang, Ming Zhang, Teng Liu, Xin-Lan Qu
International journal of clinical and experimental pathology 2015
Expression of Interferon γ by Decidual Cells and Natural Killer Cells at the Human Implantation Site: Implications for Preeclampsia, Spontaneous Abortion, and Intrauterine Growth Restriction
CP Chen, L Piao, X Chen, J Yu, R Masch, F Schatz, CJ Lockwood, SJ Huang
Reproductive sciences (Thousand Oaks, Calif.) 2015
Arterial Disorders
A Berbari, G Mancia
2015

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