Effect of pentoxifylline on vascular endothelial growth factor C and flk-1 expression on endometrial implants in the rat endometriosis model

Fertil Steril. 2010 Mar 1;93(4):1316-23. doi: 10.1016/j.fertnstert.2008.10.056. Epub 2009 Jan 14.

Abstract

Objective: To investigate the effects of pentoxifylline, on vascular endothelial growth factor (VEGF)-C and flk-1 expression in the rat endometriosis model.

Design: Prospective, randomized, placebo-controlled study.

Setting: Academic institution.

Animal(s): Twenty Wistar rats with surgically induced endometriosis.

Intervention(s): Animals were evaluated after surgical induction of endometriosis and random allocation to a group that received pentoxifylline and a control group that received NaCl 0.9%, for 3 weeks. At the end of the treatment period the animals were killed and the implants evaluated macroscopically as well as by immunohistochemistry.

Main outcome measure(s): Morphologic changes of the endometriotic implants; and evaluation of VEGF-C and flk-1 expression by a semiquantitative analysis (HSCORE) for the intensity of immunohistochemical reactivity.

Result(s): A significant reduction was observed in the mean volume of the endometriotic implants per animal in the treatment group as compared with the control group. There was a significant reduction not only in the mean volume of implants per animal but also in the mean number of implants per animal after treatment. By immunohistochemical evaluation (HSCORE), there was a significant reduction in VEGF-C expression after treatment in all areas examined. A significant reduction of flk-1 expression was also noted in the glandular compartment after treatment but not in the epithelial surface or stroma.

Conclusion(s): Pentoxifylline may cause suppression of endometriotic lesions by suppressing angiogenesis through VEGF-C and flk-1 expression.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Disease Models, Animal*
  • Endometriosis / drug therapy
  • Endometriosis / metabolism*
  • Endometriosis / surgery
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Endometrium / transplantation*
  • Female
  • Infertility, Female / drug therapy
  • Infertility, Female / metabolism
  • Infertility, Female / surgery
  • Pentoxifylline / pharmacology*
  • Prospective Studies
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Transplants
  • Vascular Endothelial Growth Factor C / biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis*

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor Receptor-2
  • Pentoxifylline