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 |
---|---|---|
The Ubiquitin Ligase ASB4 Promotes Trophoblast Differentiation through the Degradation of ID2
WH Townley-Tilson, Y Wu, JE Ferguson, C Patterson, C Oudejans |
PloS one | 2014 |
LIMK1 Regulates Human Trophoblast Invasion/Differentiation and Is Down-Regulated in Preeclampsia
Y Zhou, A Yuge, AM Rajah, G Unek, PF Rinaudo, E Maltepe |
The American Journal of Pathology | 2014 |
Elastin-derived peptides stimulate trophoblast migration and invasion: a positive feedback loop to enhance spiral artery remodelling
M Desforges, LK Harris, JD Aplin |
Molecular Human Reproduction | 2014 |
Wnt-Dependent T-Cell Factor-4 Controls Human Etravillous Trophoblast Motility
G Meinhardt, S Haider, P Haslinger, K Proestling, C Fiala, J Pollheimer, M Knöfler |
Endocrinology | 2014 |
Decidual natural killer cell receptor expression is altered in pregnancies with impaired vascular remodeling and a higher risk of pre-eclampsia
AE Wallace, GS Whitley, B Thilaganathan, JE Cartwright |
Journal of leukocyte biology | 2014 |
Oxygen Modulates Human Decidual Natural Killer Cell Surface Receptor Expression and Interactions with Trophoblasts
AE Wallace, SS Goulwara, GS Whitley, JE Cartwright |
Biology of reproduction | 2014 |
Antiphospholipid antibodies and the placenta: a systematic review of their in vitro effects and modulation by treatment
M Tong, CA Viall, LW Chamley |
Human Reproduction Update | 2014 |
HCMV Infection of Human Trophoblast Progenitor Cells of the Placenta Is Neutralized by a Human Monoclonal Antibody to Glycoprotein B and Not by Antibodies to the Pentamer Complex
M Zydek, M Petitt, J Fang-Hoover, B Adler, L Kauvar, L Pereira, T Tabata |
Viruses | 2014 |
Trophoblast retrieval and isolation from the cervix (TRIC) for noninvasive prenatal screening at 5 to 20 weeks of gestation
JM Bolnick, BA Kilburn, S Bajpayee, N Reddy, R Jeelani, B Crone, N Simmerman, M Singh, MP Diamond, DR Armant |
Fertility and Sterility | 2014 |
Increased angiogenic factor secretion by decidual natural killer cells from pregnancies with high uterine artery resistance alters trophoblast function
AE Wallace, R Fraser, S Gurung, SS Goulwara, GS Whitley, AP Johnstone, JE Cartwright |
Human Reproduction | 2014 |
The multidrug-resistance transporter ABCB5 is expressed in human placenta
ER Volpicelli, C Lezcano, Q Zhan, SD Girouard, DW Kindelberger, MH Frank, NY Frank, CP Crum, GF Murphy |
International Journal of Gynecological Pathology | 2014 |
Noninvasive and Quantitative Assessment of In Vivo Fetomaternal Interface Angiogenesis Using RGD-Based Fluorescence
M Keramidas, J Lavaud, F Sergent, P Hoffmann, S Brouillet, JJ Feige, JL Coll, N Alfaidy |
BioMed Research International | 2014 |
Angiogenin Expression during Early Human Placental Development; Association with Blood Vessel Formation
N Pavlov, JL Frendo, J Guibourdenche, SA Degrelle, D Evain-Brion, J Badet |
BioMed Research International | 2014 |
Signaling pathways in mouse and human trophoblast differentiation: a comparative review
F Soncin, D Natale, MM Parast |
Cellular and Molecular Life Sciences | 2014 |
Oxygen regulates human cytotrophoblast migration by controlling chemokine and receptor expression
A Schanz, K Red-Horse, AP Hess, DM Baston-Büst, C Heiss, JS Krüssel |
Placenta | 2014 |
p63 Inhibits Extravillous Trophoblast Migration and Maintains Cells in a Cytotrophoblast Stem Cell-Like State
Y Li, M Moretto-Zita, S Leon-Garcia, MM Parast |
The American Journal of Pathology | 2014 |
Review: The ADAM metalloproteinases – Novel regulators of trophoblast invasion?
J Pollheimer, V Fock, M Knöfler |
Placenta | 2014 |
Expression of Gadd45α in human early placenta and its role in trophoblast invasion
X Liu, H Mu, X Luo, X Xiao, Y Ding, N Yin, Q Deng, H Qi |
Placenta | 2014 |
Development of the hemochorial maternal vascular spaces in the placenta through endothelial and vasculogenic mimicry
A Rai, JC Cross |
Developmental Biology | 2014 |
An integrative view on the physiology of human early placental villi
B Huppertz, D Ghosh, J Sengupta |
Progress in Biophysics and Molecular Biology | 2014 |
Tetrabromobisphenol A activates inflammatory pathways in human first trimester extravillous trophoblasts in vitro
HR Park, PW Kamau, C Korte, R Loch-Caruso |
Reproductive Toxicology | 2014 |
Evaluation of inflammatory mediators in the deciduas of pregnant women with pre-eclampsia/eclampsia
AB Peixoto, EA Júnior, JU Ribeiro, DB Rodrigues, EC Castro, TM Caldas, VR Júnior |
Journal of Maternal-Fetal and Neonatal Medicine | 2014 |
Discovery of a Cell: Reflections on the Checkered History of Intermediate Trophoblast and Update on its Nature and Pathologic Manifestations
RJ Kurman, IM Shih |
International Journal of Gynecological Pathology | 2014 |
Hyperglycemia impairs cytotrophoblast function via stress signaling
C Cawyer, D Horvat, D Leonard, SR Allen, RO Jones, DC Zawieja, TJ Kuehl, MN Uddin |
American Journal of Obstetrics and Gynecology | 2014 |
Calcitonin gene- and parathyroid hormone-related peptides in normotensive and preeclamptic pregnancies: a nested case–control study
S Yadav, YS Yadav, MM Goel, U Singh, SM Natu, MP Negi |
Archives of Gynecology and Obstetrics | 2014 |
Pathobiology of Human Disease
S Akilesh |
Pathobiology of Human Disease | 2014 |
A new marker set that identifies fetal cells in maternal circulation with high specificity: Fetal cell identification in maternal blood
L Hatt, M Brinch, R Singh, K Møller, RH Lauridsen, JM Schlütter, N Uldbjerg, B Christensen, S Kølvraa |
Prenatal Diagnosis | 2014 |
Differential Methylation of Genes Associated with Cell Adhesion in Preeclamptic Placentas
L Anton, AG Brown, MS Bartolomei, MA Elovitz, C Oudejans |
PloS one | 2014 |