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The human placenta remodels the uterus by using a combination of molecules that govern vasculogenesis or leukocyte extravasation.

Abstract：

:After fertilization, the next major hurdle for human reproduction is trophoblast differentiation, which is required for implantation, followed in lockstep by rapid assembly of these embryonic cells into a functional placenta. During this process, cytotrophoblast stem cells invade the uterus, anchoring the conceptus to the mother and establishing blood flow to the placenta. Cytotrophoblast invasion is actually a differentiation process that yields cells with many unusual attributes, that is, their tumor-like ability to invade the uterus and engraft maternal blood vessels. We discovered that once cytotrophoblasts commit to invasion they turn on expression of adhesion receptors characteristic of endothelium. They also begin to express and activate matrix metalloproteinase-9. Together, these phenotypic changes facilitate invasion while enabling cytotrophoblasts to present an endothelium-like surface to maternal blood. Currently, we are trying to understand the factors that play a role in cytotrophoblast differentiation/invasion. In keeping with the vascular characteristics that differentiated cytotrophoblasts assume, our recent data suggest that the key regulators include an unusual subset of vascular endothelial growth factor family members that play important roles in conventional vasculogenesis/angiogenesis. Surprisingly, we also discovered that these cells express functional l-selectin, which mediates neutrophil rolling and tethering, under shear stress, on inflamed endothelium. Trophoblast l-selectin likely interacts with carbohydrate selectin ligands that are upregulated on uterine glandular epithelium during the window of receptivity. Together, these data suggest that differentiating cytotrophoblasts have co-opted portions not only of vasculogenesis, but also of the process that facilitates leukocyte emigration from the blood into tissues, additional evidence of these cells' amazing plasticity.

journal_name

Ann N Y Acad Sci

journal_title

Annals of the New York Academy of Sciences

authors

Zhou Y,Genbacev O,Fisher SJ

doi

10.1111/j.1749-6632.2003.tb03211.x

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

73-83

eissn

0077-8923

issn

1749-6632

journal_volume

995

pub_type

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The human placenta remodels the uterus by using a combination of molecules that govern vasculogenesis or leukocyte extravasation.