E-cadherin expression and bromodeoxyuridine incorporation during development of ovarian inclusion cysts in age-matched breeder and incessantly ovulated CD-1 mice.

Abstract

Background: Epithelial ovarian cancer risk increases in women who have experienced high lifetime ovulation numbers. We have shown female CD-1/Swiss Webster mice subjected to incessant ovulation for 8 months develop ovarian inclusion cysts similar to serous cystadenomas. We therefore hypothesized that incessant ovulation for 12 months might lead to epithelial ovarian carcinoma. Methods: Ovaries 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. Epithelial cell samples from the ovarian surface epithelium (OSE), rete ovarii and cyst epithelia were obtained by laser-capture microdissection from IO ovaries and E-cadherin and ß-actin expression determined by quantitative RT-PCR. Results: Inclusion cysts developed with age in both BR and IO ovaries. Most cysts were connected to the ovarian hilus. Three cortical cysts were observed in ten IO ovaries and one in ten BR ovaries. However no neoplasia was observed. Low concentrations of E-cadherin mRNA, but no protein immuno-staining were measured in OSE. Conversely, no E-cadherin mRNA could be detected in rete ovarii, despite strong membrane immuno-staining and similar b-actin mRNA concentrations to those measured in OSE. High concentrations of E-cadherin mRNA and variable E-cadherin immunoreactivity were measured in inclusion cyst cells. Very few BrdU-labeled cells were observed in rete ovarii at any age, whereas 0.4-1.5% of OSE cells and 0.8-1.8% of cyst cell nuclei incorporated BrdU. Conclusions: We conclude incessant ovulation alone for an extended length of time does not lead to transformation of cyst cells in CD-1 mice. The rete ovarii tubules dilate with age in this mouse strain, irrespective of total ovulation burden.