Induction of Endometriosis in a Menstruating Mouse Model (Mus musculus): A Translational Animal Disease Model.

Abstract

Improved animal models of endometriosis are needed to accurately represent the pathophysiology of human disease and identify new therapeutic targets that do not compromise fertility. There is tremendous heterogeneity among published rodent models of endometriosis, and the etiology and pathogenesis of endometriosis remain undetermined. The vast majority of endometriosis is found in menstruating women; however, no published mouse models have induced endometriosis in a menstruating mouse, further limiting our understanding of the disease. Our goal was to develop a novel, translationally relevant mouse model of endometriosis in a menstruating mouse by transplanting donor menstrual endometrium into the peritoneal cavity of menstruating, immunocompetent, intact recipients. We initially compared 4 different experimental groups to optimize implanted menstrual tissue type and method of implantation into intact, normally cycling recipient mice. To further optimize this model, a novel fifth experimental group was compared in which discrete pieces of menstrual donor endometrium were implanted via laparoscopy into menstruating recipient mice. Lesions were confirmed to be endometriosis based on histopathology. The use of laparoscopy to place discrete fragments of menstrual phase endometrium intraabdominally was the most effective method for induction of endometriosis. This method was just as effective when used to induce endometriosis in menstruating recipient mice. Menstruating mice returned to normal estrus cyclicity after induction of disease, which can allow for assessment of therapeutic interventions on fertility. This is a novel translationally relevant mouse model of endometriosis in a menstruating mouse that can be used to explore and elucidate the etiology and pathogenesis of this disease.