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Lookup NU author(s): Dr Gendie Lash
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Context: Trophoblast invasion of the uterus is regulated by local microenvironmental factors. Objective: Because certain conditions may affect uterine glucose levels during placentation, the aim of this study was to determine the effect of glucose concentration on trophoblast invasion. Results: Compared with incubation in 0.2 and 2.5mM glucose, a 24-h incubation in increasing glucose concentrations (5 and 10 mM) resulted in up to a 62% inhibition (P < 0.01) of the in vitro invasiveness of immortalized HTR-8/SVneo trophoblasts. This decreased invasiveness in 5 and 10 mM glucose was paralleled by inhibition of a plasminogen activator (PA) activity corresponding to active urokinase-type PA (uPA). Inhibition of pro-uPA binding to the uPA receptor decreased the invasiveness of cells incubated in 0.2 and 2.5 mM glucose to levels observed in cells incubated in higher glucose concentrations (P < 0.05). Gelatin zymography and Western blot analysis revealed that the levels of matrix metalloproteinase-2 and -9, PA inhibitor-1, and uPA receptor were unaffected by glucose. Glucose transporter-1 levels were 26 and 34% higher in cells cultured in 2.5 and 0.2 mM glucose, respectively, vs. 5 or 10 mM glucose (P < 0.05). In contrast, glucose transporter-3 levels were not affected by incubation in various glucose concentrations. Conclusions: These findings indicate that high glucose concentrations inhibit the invasiveness of HTR-8/SVneo cells by preventing uPA activation. Therefore, through its effects on uPA activity, glucose may be an important regulator of trophoblast invasiveness during implantation and placentation. Copyright © 2005 by The Endocrine Society.
Author(s): Belkacemi L, Lash GE, Macdonald-Goodfellow SK, Caldwell JD, Graham CH
Publication type: Article
Publication status: Published
Journal: Journal of Clinical Endocrinology and Metabolism
ISSN (print): 0021-972X
ISSN (electronic): 1945-7197
Publisher: The Endocrine Society
PubMed id: 15886249
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