Pathologic characteristics of ovarian hemorrhagic polycyst in estrogen receptor-alpha (ERα) knockout mice and roles of erα in hemorrhagic polycyst

Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy causing anovulation in women of childbearing age. It has been well established that estrogen receptor-alpha knockout (ERαKO) mice display sevERαl pathologic ovarian phenotypes of PCOS. The aims of this study were to determine ovarian pathology in new ERαKO mice using a CreloxP approach and intrα-ovarian ERα function as regulating key aspects of PCOS. Methods: ERαKO mice, which were deficient in exon 3 of the ERα gene, were used. Immunohistochemical studies were done on ovaries of control and ERαKO mice using antibodies specific to ERα, ERβ, inhibin-α, and a-smooth muscle actin (SMA), as well as histochemical staining using Sudan black-B. Results: All ovaries of ERαKO mice were larger than control mouse ovaries and displayed a disrupted theca-interstitial tissue organization, multiple atretic follicles and multiple hemorrhagic cysts. None of the ERαKO mouse ovaries showed a corpus luteum. In addition, heavy deposition of Sudan black-B positive foamy cells was seen. The theca externa of preantral immature follicles and hemorrhagic cysts showed strong expression of α-SMA. Conclusions: ERαKO mice show hemorrhagic polycystic ovaries and hyperplasia of the theca externa. This study demonstrates that the ERα is the functional key to the pathogenesis of PCOS.