Strain-differences in proliferative activity of uterine endometrial cells in Donryu and Fischer 344 rats

Strain differences in proliferative activities of uterine endometrial cells were sequentially investigated in Donryu and Fischer 344 (F344) rats until 52 weeks of age. At 13 and 26 weeks of age, when all rats showed a normal estrous cycle, histological findings for the endometrium at each estrous stage were similar in both strains. Mitoses of epithelial cells were frequently observed during the proestrous and metestrous stages, and especially in the latter, but were very few in the estrous stage. The bromodeoxyuridine(BrdU)-labeling indices coincided with the histological findings, the results indicating a peak of cell proliferative activity in the metestrous stage. In Donryu rats, estrous cycle abnormalities increased age-dependently after 26 weeks of age, and almost all animals showed persistent estrus at 52 weeks of age. At 39 and 52 weeks of age, the rats showing persistent estrus displayed similar vaginal smears and histological findings to those of younger rats in the estrous stage, but the BrdU-labeling indices of epithelial cells were age-dependently increased. In contrast, vaginal smear of F344 rats indicated a normal estrous cycle at all ages, with no changes in BrdU-labeling being observed. Previously, we reported that the Donryu rat is a high incidence strain in terms of spontaneous development of endometrial adenocarcinomas, this being related to an age-dependent hormonal imbalance, characterized in particular by an increased estrogen/progesterone ratio. The F344 rat in contrast is a low incidence strain. The present results thus indicate that a constant high-level of proliferative activity of epithelial cells may play an important role, together with an age-related hormonal imbalance, in the spontaneous development of endometrial carcinomas in Donryu rats.