Effects of angiogenesis inhibitor TNP-470 on the development of uterine adenomyosis in mice.

Objective: To investigate the effects of angiogenesis inhibitor TNP-470 on uterine microvessels in mice. Pituitary grafting frequently induced uterine adenomyosis.

Design: In vivo experimental study.

Setting: Department of Biological Sciences, University of Tokyo and Medical Research Institute, Tokyo Medical and Dental University.

Animal(s): SHN mice, which are known to develop uterine adenomyosis spontaneously, and also very soon after pituitary grafting.

Intervention(s): Immunohistochemical study on uterine blood vessels using an antibody to von Willebrand factor in pituitary gland-implanted mice with or without TNP-470.

Main Outcome Measure(s): Reduced incidence of uterine adenomyosis.

Result(s): Twelve of 15 mice developed uterine adenomyosis with dilated blood vessels, but none of the TNP-470-treated mice with shrunken microvessels. The number of bromodeoxyuridine immunoreactive cells and activities of thymidylate synthase and thymidine kinase in uterine tissues were markedly reduced in TNP-470-treated mice.

Conclusion(s): TNP-470, a potent inhibitor of the development of vascular endothelium, reduced the development of endometrial blood vessels resulting in a lowered incidence of uterine adenomyosis induced by pituitary grafting in mice, and reduced the increase in S-phase cells and enzyme activity for pyrimidine nucleotide synthesis.