Molecular Organization of Tight and Adherens Junctions in the Human Placental Vascular Tree

Leach, Lopa; Lammiman, M. J.; Babawale, Michael; Hobson, S. A.; Bromilou, B.; Lovat, S.; Simmonds, Michael J.

doi:10.1053/plac.2000.0541

Cited by 61 publications

(52 citation statements)

References 23 publications

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“…Because of the relative sizes of the containing villi it is tempting to view this as a maturational process, and continuing angiogenic remodeling may serve to connect the arterio-venous circuit to that in the parent intermediate villus in a more efficient fashion. The observation that the junctional complexes linking adjacent endothelial cells within terminal villi demonstrate a molecular phenotype similar to that seen in the first trimester, suggesting they are relatively immature and plastic compared to the larger vessels of the villous tree, is consistent with this hypothesis (Leach et al 2000, Leach 2002). …”

Section: Morphological Aspects Of Vascular Developmentsupporting

confidence: 66%

Regulation of vascular growth and function in the human placenta

Burton¹,

Charnock-Jones²,

Jauniaux³

2009

Reproduction

301

189

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During the course of 9 months, the human placenta develops into a highly vascular organ. Vasculogenesis starts during the third week post-conception. Hemangioblastic cell cords differentiate in situ from mesenchymal cells in the villous cores, most probably under the influence of vascular endothelial growth factor (VEGFA) secreted by the overlying trophoblast. The cords elongate through proliferation and cell recruitment, and connect with the vasculature of the developing fetus. A feto-placental circulation starts around 8 weeks of gestation. Elongation of the capillaries outstrips that of the containing villi, leading to looping of the vessels. The obtrusion of both capillary loops and new sprouts results in the formation of terminal villi. Branching and non-branching angiogenesis therefore play key roles in villous morphogenesis throughout pregnancy. Maternal circulating levels of VEGFA and placental growth factor vary across normal pregnancy, and in complicated pregnancies. Determining the impact of these changes on placental angiogenesis is difficult, as the relationship between levels of factors in the maternal circulation and their effects on fetal vessels within the placenta remains unclear. Furthermore, the trophoblast secretes large quantities of soluble receptors capable of binding both growth factors, influencing their bioavailability. Villous endothelial cells are prone to oxidative stress, which activates the apoptotic cascade. Oxidative stress associated with onset of the maternal circulation, and with incomplete conversion of the spiral arteries in pathological pregnancies, plays an important role in sculpting the villous tree. Suppression of placental angiogenesis results in impoverished development of the placenta, leading ultimately to fetal growth restriction. Reproduction (2009) 138 895-902

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Section: Morphological Aspects Of Vascular Developmentsupporting

confidence: 66%

Regulation of vascular growth and function in the human placenta

Burton¹,

Charnock-Jones²,

Jauniaux³

2009

Reproduction

301

189

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“…Occludin but not ZO-1 is found in first trimester villous trophoblast populations [45]. Continuous staining suggests true tight junctions are not present.…”

Section: Tight Junction Proteinsmentioning

confidence: 91%

Adhesion Molecules in Human Trophoblast – A Review. I. Villous Trophoblast

Aplin¹,

Jones²,

Harris³

2009

Placenta

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In the placental villus, cells attach to basement membrane via integrin α6β4 and adhere both laterally and apically to their neighbours. The most prominent adhesive specialisation seen in the electron microscope is the desmosome, which connects cytotrophoblast cells (CTB) laterally and also contributes to the attachment of CTB to the overlying syncytium.However, numerous cadherins and other junctional proteins are also present in the corresponding plasma membrane domains, indicating a multiplicity of adhesive interactions.Integrins, tight junction components and cadherins are all found in the syncytial microvillous membrane, perhaps reflecting its ability to form intersyncytial bridges. There is a wide gulf to be filled between molecular anatomy and functional studies, with much to be learned about the role of adhesion molecules in regulating villous epithelial integrity, homeostasis and growth.3

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“…They play a key role in placental vascular development in humans, as shown by the early expression of these molecules in haemangioblasts of the first trimester placenta [10]. Differential expression of these molecules in normal and histamine-perfused term placentae indicates their importance in regulating vascular permeability and plasticity [11,12]. We have previously shown that the loss of junctional VE-cadherin and β-catenin is a very early event in VEGF-induced angiogenesis in human umbilical vein cells [13].…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial cadherin and �-catenin in human fetoplacental vessels of pregnancies complicated by Type 1 diabetes: associations with angiogenesis and perturbed barrier function

et al. 2004

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Aims/hypothesis. Increased angiogenesis of fetoplacental vessels is a feature of pregnancies complicated by Type 1 diabetes mellitus, but the underlying molecular mechanisms are unknown. This investigation tests whether the diabetic maternal environment alters the phenotypic expression of placental vascular endothelial cadherin and β-catenin, which have been implicated as key molecules in barrier formation and angiogenesis in the endothelium. Methods. Term placental microvessels from normal pregnancies (n=8) and from those complicated by Type 1 diabetes (n=8) were perfused with 76-M r dextran tracers (1 mg/ml) and subjected to immunocytochemistry, immunoblotting and microscopy. Junctional integrity, localisation and phosphorylation were investigated along with total protein levels of vascular endothelial cadherin, β-catenin and vascular endothelial growth factor. Stereological sampling and estimation tools were used to quantify aspects of angiogenesis and endothelial proliferation. Results. In the Type 1 diabetic placentae, junctional localisations of vascular endothelial cadherin and β-catenin altered significantly, with more than 50% of microvessels showing complete loss of immunoreactivity and with no overall loss of total protein. Tracer leakage was associated with these vessels. There was a two-to three-fold increase in vessels showing junctional phospho-tyrosine immunoreactivity and hyperphosphorylated β-catenin. Vascular endothelial growth factor levels were higher in these placentae. A fourfold increase in endothelial proliferation was observed, along with an increase in total length of capillaries without any change in luminal diameter. Conclusions/interpretation. Molecular perturbations of vascular endothelial cadherin and β-catenin occur in fetoplacental vessels of pregnancies complicated by Type 1 diabetes. Phosphorylation and loss of these molecules from the adherens junctional domains may be influenced in part by the elevated levels of vascular endothelial growth factor in the placenta. Perturbations of the junctional proteins may explain the observed breach in barrier integrity and may contribute to the mechanisms that drive proliferation and increases in capillary length.

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Molecular Organization of Tight and Adherens Junctions in the Human Placental Vascular Tree

Cited by 61 publications

References 23 publications

Regulation of vascular growth and function in the human placenta

Regulation of vascular growth and function in the human placenta

Adhesion Molecules in Human Trophoblast – A Review. I. Villous Trophoblast

Vascular endothelial cadherin and �-catenin in human fetoplacental vessels of pregnancies complicated by Type 1 diabetes: associations with angiogenesis and perturbed barrier function

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