Inhibition of human trophoblast invasiveness by high glucose concentrations

J Clin Endocrinol Metab. 2005 Aug;90(8):4846-51. doi: 10.1210/jc.2004-2242. Epub 2005 May 10.

Abstract

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 2.5 mm 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Transformed
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Dose-Response Relationship, Drug
  • Extracellular Matrix / metabolism
  • Female
  • Glucose / pharmacology*
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Monosaccharide Transport Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Receptors, Cell Surface / metabolism
  • Receptors, Urokinase Plasminogen Activator
  • Trophoblasts / cytology*
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Monosaccharide Transport Proteins
  • Nerve Tissue Proteins
  • PLAUR protein, human
  • Plasminogen Activator Inhibitor 1
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • SLC2A1 protein, human
  • SLC2A3 protein, human
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinases
  • Glucose