Effects of angiogenesis inhibitor TNP-470 on the development of uterine adenomyosis in mice  Ying-Fang Zhou, M.D., Takao Mori, Ph.D., Hideki Kudo, M.D., Rei Asakai, M.D., Shuji Sassa, B.S., Shinobu Sakamoto, M.D., Ph.D.  Fertility and Sterility  Volume 80, Pages 788-794 (September 2003) DOI: 10.1016/S0015-0282(03)00988-9

FIGURE 1 Immunohistochemical staining using von Willebrand factor (vWF) in the uteri of SHN mice. Uterine sections from pituitary-grafted mice (B: PG-control group) demonstrate increased numbers of dilated venules in the endometrium and mild adenomyosis near the mesometrium (arrowhead indicates a focus of adenomyosis) compared with normal-control mice (A: Normal-control group), i.e. numerous small microvessels in the endometrium. Uteri of TNP-470-treated mice show shrinkage of microvessels and no adenomyotic change (C) (Original magnification x 72). Representative uterine adenomyosis (D), invasion of endometrial tissues into the connective tissue spaces between inner and outer layers of the myometrium is evident in mice at age 300 days (different from the present sample; referred from Acta Anat 159:204, 1997). Zhou. Angiogenesis inhibitor TNP-470 on mouse adenomyosis. Fertil Steril 2003. Fertility and Sterility 2003 80, 788-794DOI: (10.1016/S0015-0282(03)00988-9)

FIGURE 2 Parameters of blood vessels in the endometrium and myometrium of pituitary-grafted mice with or without TNP-470 treatment (TNP-470 group and PG-control group, respectively). Pituitary grafting was performed at 7 weeks of age. The mice in the TNP-470 group were given subcutaneous injections of TNP-470 (0.5 mg/50 μl DMSO/30 g body weight) twice a week from 7 to 13 weeks of age. PG-control group: open bars, TNP-470 group: hatched bars. Values are the mean ± bSEM; **P<0.01, *P<0.05. Zhou. Angiogenesis inhibitor TNP-470 on mouse aderomyosis. Fertil Steril 2003. Fertility and Sterility 2003 80, 788-794DOI: (10.1016/S0015-0282(03)00988-9)

FIGURE 3 In vivo bromodeoxyuridine (BrdU) labeling in the endometrium (luminal epithelial cells, gland epithelial cells and stromal cells) and inner myometrium (smooth muscle cells) of pituitary-grafted mice with or without TNP-470 treatment. Six sections of each uterus were randomly chosen and BrdU-immunoreactive (S-phase) cells were counted in 400 cells per section. The results were expressed in terms of BrdU-immunoreactive cells as a percentage of total cells. PG-control group: open bars, TNP-470 group: hatched bars. Values are mean ± SEM; **P<0.01, *P<0.05. Zhou. Angiogenesis inhibitor TNP-470 on mouse adenomyosis. Fertil Steril 2003. Fertility and Sterility 2003 80, 788-794DOI: (10.1016/S0015-0282(03)00988-9)