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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Placental Ischemia and Resultant Phenotype in Animal Models of Preeclampsia
B LaMarca, LM Amaral, AC Harmon, DC Cornelius, JL Faulkner, MW Cunningham |
Current Hypertension Reports | 2016 |
Pathophysiology of preeclampsia: an angiogenic imbalance and long-lasting systemic vascular dysfunction
T Tomimatsu, K Mimura, M Endo, K Kumasawa, T Kimura |
Hypertension Research | 2016 |
Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells
M Pinto, P Sotomayor, G Carrasco-Avino, A Corvalan, G Owen |
International journal of molecular sciences | 2016 |
Notch1 controls development of the extravillous trophoblast lineage in the human placenta
S Haider, G Meinhardt, L Saleh, C Fiala, J Pollheimer, M Knöfler |
Proceedings of the National Academy of Sciences | 2016 |
Local and systemic factors and implantation: what is the evidence?
C Fox, S Morin, JW Jeong, RT Scott, BA Lessey |
Fertility and Sterility | 2016 |
Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission
T Tabata, M Petitt, H Puerta-Guardo, D Michlmayr, C Wang, J Fang-Hoover, E Harris, L Pereira |
Cell Host & Microbe | 2016 |
Umbilical cord plasma interferon-induced protein 10 (IP-10) and interferon-induced T-cell alpha chemoattractant (ITAC) levels are lower in women with severe preeclampsia
P Chedraui, EJ Solís, FR Pérez-López, F Schatz, U Kayisli, GS Escobar, R Loja-Chango, L Hidalgo, CJ Lockwood |
Journal of Perinatal Medicine | 2016 |
Increased expression of fatty acid binding protein 4 in preeclamptic Placenta and its relevance to preeclampsia
Y Yan, H Peng, P Wang, H Wang, M Dong |
Placenta | 2016 |
Potential role of epigenetic mechanisms in regulation of trophoblast differentiation, migration, and invasion in the human placenta
HR Kohan-Ghadr, L Kadam, C Jain, DR Armant, S Drewlo |
Cell adhesion & migration | 2016 |
Attenuation of hyperglycemia-induced apoptotic signaling and anti-angiogenic milieu in cultured cytotrophoblast cells
C Cawyer, SH Afroze, N Drever, S Allen, R Jones, DC Zawieja, T Kuehl, MN Uddin |
Hypertension in Pregnancy | 2016 |
First trimester trophoblasts forming endothelial-like tubes in vitro emulate a ‘blood vessel development’ gene expression profile
AR Highet, S Buckberry, BT Mayne, SM Khoda, T Bianco-Miotto, CT Roberts |
Gene Expression Patterns | 2016 |
Integrin α4-positive human trophoblast progenitors: functional characterization and transcriptional regulation
O Genbacev, N Larocque, K Ona, A Prakobphol, T Garrido-Gomez, M Kapidzic, A Bárcena, M Gormley, SJ Fisher |
Human Reproduction | 2016 |
Intrauterine trophoblast migration: A comparative view of humans and rodents
JF Silva, R Serakides |
Cell adhesion & migration | 2016 |
Tumor-homing peptides as tools for targeted delivery of payloads to the placenta
A King, C Ndifon, S Lui, K Widdows, VR Kotamraju, L Agemy, T Teesalu, JD Glazier, F Cellesi, N Tirelli, JD Aplin, E Ruoslahti, LK Harris |
Science Advances | 2016 |
Placental Hypomethylation Is More Pronounced in Genomic Loci Devoid of Retroelements
A Chatterjee, EC Macaulay, EJ Rodger, PA Stockwell, MF Parry, HE Roberts, TL Slatter, NA Hung, CJ Devenish, IM Morison |
G3: Genes|Genomes|Genetics | 2016 |
Acute kidney injury in pregnancy
C Praveen, A Kaul, RK Sharma |
Clinical Queries Nephrology | 2016 |
Macrophage polarisation affects their regulation of trophoblast behaviour
RJ Buckley, GS Whitley, IE Dumitriu, JE Cartwright |
Placenta | 2016 |
Advances in Experimental Medicine and Biology
C Bosco, E Díaz |
Advances in experimental medicine and biology | 2016 |
Stromal Cell-Derived Factor 2: A Novel Protein that Interferes in Endoplasmic Reticulum Stress Pathway in Human Placental Cells
AR Lorenzon-Ojea, CR Guzzo, M Kapidzic, SJ Fisher, E Bevilacqua |
Biology of reproduction | 2016 |
Fetal microchimerism and prenatal diagnostic of genetic disorders
TM Lutsenko |
Cell and Organ Transplantology | 2016 |
Establishment of the Human Uteroplacental Circulation: A Historical Perspective
K Degner, RR Magness, DM Shah |
Reproductive sciences (Thousand Oaks, Calif.) | 2016 |
Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth - SYDE1 regulates placental cell migration and invasion: SYDE1 regulates placental development
HF Lo, CY Tsai, CP Chen, LJ Wang, YS Lee, CY Chen, CT Liang, ML Cheong, H Chen |
The Journal of Pathology | 2016 |
Obstetrie en gynaecologie
MJ Heineman, JL Evers, LF Massuger, EA Steegers |
2016 |