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

Fertility and Sterility, ISSN: 0015-0282, Vol: 80, Issue: SUPPL. 2, Page: 788-794
2003
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To investigate the effects of angiogenesis inhibitor TNP-470 on uterine microvessels in mice. Pituitary grafting frequently induced uterine adenomyosis. In vivo experimental study. Department of Biological Sciences, University of Tokyo and Medical Research Institute, Tokyo Medical and Dental University. SHN mice, which are known to develop uterine adenomyosis spontaneously, and also very soon after pituitary grafting. Immunohistochemical study on uterine blood vessels using an antibody to von Willebrand factor in pituitary gland-implanted mice with or without TNP-470. Reduced incidence of uterine adenomyosis. 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. 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.

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