Effects of mifepristone (RU486) treatment on the development of uterine adenomyosis induced by pituitary grafting in mice

To evaluate the effects of mifepristone (RU486) on the development of uteri ne adenomyosis induced by pituitary grafting (PG), 3 groups of mice receivi ng pituitary grafts at 7 weeks of age were given RU486 in food (20mg/kg cho w) from 3-14 (RU486-3 group) or 10-14 (RU486-10 group) weeks of age, or wer e given no further treatment (PG control group), respectively. All the mice were killed at 14 weeks of age. The uterine weight was significantly decre ased in both RU486-treated groups compared with the PG control group. The i ncidence of adenomyosis was also decreased significantly in both the RU486- 3 group (0/10 mice) and RU486-10 group (2/10 mice) compared with the PG con trol group (7/9 mice). To look for vascular changes in the uterine tissues, which have been reported to be related to the development of adenomyosis, immunohistochemical staining of von Willebrand factor in the blood vessels was performed. The mean surface area and minor axis of blood vessels in the uterus were thereby found to be significantly decreased in the RU486-10 gr oup compared to the PG control group. The results clearly indicated that RU 486, a potent antiprogestin, could inhibit the genesis of uterine adenomyos is in mice, and at the same time caused shrinkage of the vascular system. A s in humans, progesterone as well as the vascular system therefore appear t o be important factors in the pathogenesis of uterine adenomyosis in this m ouse model. (C) 2000 Elsevier Science Inc. All rights reserved.