Abstract
BackgroundFemale CD-1/Swiss Webster mice subjected to incessant ovulation for 8 months and 12-month breeder mice both developed ovarian inclusion cysts similar to serous cystadenomas. The majority of cysts appeared to be dilated rete ovarii tubules, but high ovulation number resulted in more cortical inclusion cysts. We hypothesized that comparison of inclusion cyst pathology in animals of the same age, but with differences in total lifetime ovulation number, might allow us to determine distinguishing characteristics of the two types of cyst.MethodsOvaries from breeder mice (BR) or females subjected to incessant ovulation (IO) were compared at 6-, 9- and 12-months of age. Ovaries were serially sectioned and cysts characterized with regard to location and histology, E-cadherin immunoreactivity and rates of BrdU incorporation.ResultsInclusion cysts developed with age in BR and IO ovaries. The majority of cysts were connected to the ovarian hilus. Two cortical inclusion cysts were observed in ten IO ovaries and one in ten BR ovaries. Low or no E-cadherin immuno-staining was seen in the OSE of all mice studied. Conversely, strong membrane immuno-staining was observed in rete ovarii epithelial cells. Variable E-cadherin immunoreactivity was seen in cells of hilar inclusion cysts, with strong staining observed in cuboidal ciliated cells and little or no staining in flat epithelial cells. Two of the three cortical cysts contained papillae, which showed E-cadherin immuno-staining at the edge of cells. However hilar and cortical cysts were not distinguishable by morphology, cell type or E-cadherin immunoreactivity. BrdU incorporation in cyst cells (1.4% [95% CI: 1.0 to 2.1]) was greater than in OSE (0.7% [95% CI: 0.4 to 1.2]) and very few BrdU-labeled cells were observed in rete ovarii at any age. Incessant ovulation significantly increased BrdU incorporation in OSE of older animals.ConclusionThese experiments confirm ovarian inclusion cysts develop with age in the CD-1 mouse strain, irrespective of total ovulation burden. We conclude longer periods of incessant ovulation do not lead to significant changes in inclusion cyst formation or steroidogenesis in CD-1 mice and inclusion cyst type can not be distinguished by morphology, cell proliferation rate or E-cadherin immunoreactivity.
Highlights
Female CD-1/Swiss Webster mice subjected to incessant ovulation for 8 months and 12month breeder mice both developed ovarian inclusion cysts similar to serous cystadenomas
Female out-bred CD-1/Swiss Webster mice were housed in two groups in a temperature- and light-controlled facility; (1) in breeding pairs (BR group) with one female housed with a male Swiss Webster mouse and (2) in a cage divided by a perforated screen, with two females housed beside, but not in contact with a single male mouse, to induce incessant ovulation (IO group) and prevent breeding [1]
Estimated ovulation numbers Total lifetime ovulation number was estimated from the records of the breeding pairs, as described previously
Summary
Female CD-1/Swiss Webster mice subjected to incessant ovulation for 8 months and 12month breeder mice both developed ovarian inclusion cysts similar to serous cystadenomas. Our previous studies demonstrated that ovaries of CD-1/ Swiss Webster mice subjected to incessant ovulation (IO) had changes suggestive of a precancerous state, such as an increased number of surface invaginations, stratification of the ovarian surface epithelium (OSE) and inclusion cyst formation [1,2]. Dilation of the rete ovarii tubules to form serous inclusion cysts occurred with age in breeding females with a much lower total ovulation number [2]. These studies compared ovaries from incessantly ovulated ovaries and breeders of different ages. We hypothesized that comparison of inclusion cyst pathology in animals of the same age, but with large differences in total lifetime ovulation number, might allow us to distinguish better between cortical and rete ovarii cysts. We measured E-cadherin expression in our model of incessant ovulation, to compare expression in the cells lining inclusion cysts with that in the OSE or rete ovarii
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