Ovarian inclusion cysts, thought to be precursor lesions for some epithelial ovarian cancers (EOC), are assumed to form from invagination of ovarian surface epithelium (OSE). We hypothesize inclusion cysts are derived from more than one epithelial source in mice. While rare cortical cysts are possibly derived from OSE invagination, large cysts connected to the ovarian hilus probably arise from dilation of the rete ovarii. We compared E-cadherin mRNA and protein expression with cell proliferation measured by bromodeoxyuridine (BrdU) incorporation, in different epithelial cell compartments of ovaries from breeder mice (BR) or female mice subjected to incessant ovulation, at 3-, 6-, 9- and 12-months of age. Incessant ovulation was induced by keeping Swiss Webster mice in cages divided by a screen. Epithelial cell samples from the OSE, rete ovarii and cyst epithelia were obtained by laser-capture microdissection from IO ovaries and E-cadherin and ߭actin expression determined by quantitative RT-PCR. E-cadherin protein and BrdU incorporation were measured by immunohistochemistry. Low concentrations of E-cadherin mRNA, but no protein immuno-staining were observed in OSE. Conversely, no E-cadherin mRNA could be detected in rete ovarii, despite strong membrane immuno-staining and similar ?-actin mRNA concentrations to those measured in OSE. High concentrations of E-cadherin and ?-actin 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 0.4-0.8% of OSE cells and 1.0-1.2% of cyst cell nuclei incorporated BrdU. We conclude normal rete ovarii cells divide infrequently and have low turnover of E-cadherin protein. OSE cells have higher rates of division and low E-cadherin mRNA expression, but the mRNA is not translated into junctional protein in this mesothelium. Cells lining cystic rete ovarii and cortical cysts have higher rates of proliferation as cysts expand. E-cadherin mRNA expression increases, but many cyst cells lose E-cadherin protein immunoreactivity. E-cadherin expression in this mouse model of ovarian inclusion cyst formation is therefore consistent with changes observed in human ovarian cystadenoma, but this protein cannot be used to determine inclusion cyst cellular origin in mice.