Effects of Ovarian Pathologies and Uterine Inflammations on Adenomyosis in Bitches

Abstract

Background: Adenomyosis is a non-neoplastic condition, characterized by the presence of endometrial glands or cells in the myometrium. Adenomyosis is defined by post-operative microscopic examination of uterine tissue and a rarely seen infertility problem in bitches. The process of transformation of healthy uterus into adenomiotic uterus is still a mystery. We aimed to determine role of ovarian pathologies and uterine inflammations on pathogenesis of uterine adenomyosis in bitches.

Cases: After ovariohysterectomy, the uteri were fixed and processed by routine methods. Sections were stained with HematoxylinEosin, Masson’s trichrome and Periodic-Acid-Schiff and immunohistochemically; with p53 protein, Ki-67, α-smooth-muscle actin, cytokeratin-CK 8, 14, 19 antibodies, estrogen and progesterone receptors by Avidin-Biotin-Complex-Peroxidase method. Histopathologically, 7 of the collected tissue samples (n = 38) were diagnosed as adenomyosis. There were unilateral (n = 6) or bilateral (n = 1) adenomyosis in which endometrial glands had broken through the myometrium, and in some cases there were fibromyoma, inflammation, papillary hyperplasia and cysts in glands. Vaginal fibroma, fibromyoma and benign mix tumor (n = 1), simple carcinoma (n = 3), carcinosarcoma (n = 3) in mammary gland were determinated histopathologically. In addition to these findings, follicular cysts (n = 4), parovarian cyst (n = 1), adenocarcinoma and Rete ovarii adenoma were diagnosed in some ovaries. The CK 19 was scored at endometrial glands (n = 2) positively and also, muscle fibers were stained positively with α-smooth-muscle actin antibody (n = 7).

Discussion: Adenomyosis is an infertility problem in adult dogs and is hard to detect with routine gynecological examinations. Adenomyosis can be seen unaccompanied by other gynecological problems such as endometritis or leiomyomas, while mammary tumors with adenomyosis have been previously reported in women and in only one case of a bitch. Little is known of the interrelationships between gross pathological and endocrine features of ovarian cysts in bitches. Due to the local hormonal imbalance, most of these ovarian tumors and cystic structures might be accompanied with uterine-vaginal and mammary gland pathologies, cystic endometrial hyperplasia-pyometra, adenomyosis, vaginal fibroma and mammary tumors. The hyperestrogenic metabolic state may promote both the invagination process and the overall spreading of adenomyosis into the myometrium. Adenomyosis is often associated with polyps, anovulation, hyperplasia without cytological atypia, and uterine leiomyoma which are produced by hyperestrogenic states. Prolactin appears to induce adenomyosis in mice and hyperprolactinemia may cause myometrial degeneration/weakness and subsequent endometrial invasion in the presence of ovarian steroids in women. Premature decline in progesterone, a problem ensues with prolactin release which can promote hyperprolactinemia or endogenous prolactin release. In addition to hormonal problems, uterine infections, immune factors and their products like cytokines and inflammatory mediators, oxidative stress and free radical metabolism also might have roles in the occurrence of adenomyosis. In the present study, four of seven adenomyotic uterine tissues had inflammation and 3 of 7 cases had pre-inflammatory changes. Changes in uterine tissues may increase cell infiltration and proliferation as well as the activity of immune cells which may promote development of adenomyosis in bitches. It is therefore possible that a defect in the p53 tumor suppressor gene may play an important role in the de novo neoplastic transformation of adenomyosis. In conclusion, adenomyosis can be observed bilaterally or unilaterally in dogs. Tissue damage under the influence of inflammation or hormonal disturbances might have a role in the occurrence of uterine adenomyosis.