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 |
---|---|---|
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 |