Optimizing a Translational Mouse Model of Endometriosis

Abstract

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. Current mouse models of endometriosis that involve ovariohysterectomy and hormone replacement preclude evaluation of fertility. Menstrual phase endometrium includes potentially important immune cells and inflammatory mediators. Our goal was to develop a novel, translationally relevant mouse model of endometriosis by transplanting donor menstrual endometrium into the peritoneal cavity of menstruating, immunocompetent, intact recipients. We tested various paradigms to determine the most effective method for establishing endometriotic lesions. Initially, 4 paradigms were tested to optimize method of induction. To enhance the model further, a novel paradigm implanted discrete menstrual phase endometrium via laparoscopy into menstruating mice. Vaginal cytology was performed to confirm continued estrus cyclicity. Potential lesions were harvested during proestrus and confirmed to be endometriosis based on histopathology. All mice demonstrated normal estrus cyclicity post induction. Incidence of endometriosis and the difference in average number of lesions across groups was compared. The use of laparoscopy to place discrete menstrual phase endometrium was the most effective method of induction of endometriosis. This method was just as effective when used to induce endometriosis in menstruating recipient mice, representing a novel translationally relevant model that can be used to assess immunologic factors and the impact of therapeutic interventions on fertility.