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.


METHODS
In vivo experimental study.


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


METHODS
SHN mice, which are known to develop uterine adenomyosis spontaneously, and also very soon after pituitary grafting.


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


METHODS
Reduced incidence of uterine adenomyosis.


RESULTS
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.


CONCLUSIONS
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.
D018194:Adenomyoma / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D003510:Cyclohexanes; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D012717:Sesquiterpenes / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000378:metabolism; D013940:Thymidylate Synthase / Q000378:metabolism; D014594:Uterine Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D000077609:O-(Chloroacetylcarbamoyl)fumagillol