Periovulatory multifocal mesothelial proliferation: a possible association with malignant transformation

This study was aimed at the identification of the site and characterization of the kinetics of tissue renewal during the repair of the ovarian surface epithelium (OSE) surrounding ovulation. Prepubescent C57BL female mice were induced hormonally either by intraperitoneal (ip) injection of pregnant mare serum gonadotropin (PMSG, 5 IU) +/- human chorionic gonadotropin (HCG, 5 IU) 46 h later, or subcutaneous (sc) diethylsilbesterol (DES) 0.1 mg or 1.0 mg in 0.5 ml corn oil, in addition to saline-injected controls. The animals were killed after various time intervals. Autoradiography was carried out on formaldehyde-fixed paraffin sections of genital organs with subsequent hematoxylin & eosin staining. The preparations were examined for nuclear [3H]thymidine incorporation (0.5 &mgr;Ci injected 1 h before killing) in the OSE, as well as the surrounding and more distal mesothelium. Surprisingly, a significant proliferative response was observed in the extra-ovarian mesothelium surrounding the uterine horns, tubes and nearby peritoneum, while the OSE proliferation rate was less than half of it. In contrast to the common notion, it seems that the expansion and repair of the OSE, associated with ovulation, is contributed mainly by its extra-ovarian mesothelial continuum. This observation may provide additional support to the multifocal theory suggested in the pathogenesis of ovarian cancer. Therefore, any search for cellular or molecular events related to malignant transformation should include the proximal and distal mesothelium in addition to the OSE.