The Development of a Mouse Model of Ovarian Endosalpingiosis

Abstract

Pelvic pain is a common presenting ailment in women often linked to ovulation, endometriosis, early pregnancy, ovarian cancer, and cysts. Clear differential diagnosis for each condition caused by these varied etiologies is difficult and may slow the delivery of therapy that, in the case of ovarian cancer, could be fatal. Ovarian endosalpingiosis, a pelvic condition typified by the presence of cystic glandular structures lined by benign tubal/salpingeal epithelium, is also associated with pelvic pain in women. The exact cellular antecedents of these epithelial lined cystic structures are not known, nor is there a known link to ovarian cancer. A mouse model of ovarian endosalpingiosis has been developed by directing a dominant-negative version of the TGF-β transcription factor, Smad2, to the ovary using the Müllerian-inhibiting substance promoter (MIS-Smad2-dn). Female mice develop an ovarian endosalpingeal phenotype as early as 3 months of age. Importantly, cysts continuous with the ovarian surface epithelial have been identified, indicating that these cyst cells may be derived from the highly plastic ovarian surface epithelial cell layer. A second transgenic mouse model that causes loss of activin action (inhibin α-subunit transgenic mice) develops similar cystic structures, supporting a TGF-β/activin/Smad2 dependence in the onset of this disease.