Animal Models in Endometriosis Part-1: Nonhuman Primate Models

Background: Endometriosis is a painful disorder in women where endometrium-like tissue exists outside of the uterine cavity. Progress on new therapies for the disorder is dependent on physiologically relevant models. Menstruation and development of spontaneous endometriosis only occur in women and Old World nonhuman primates making nonhuman primates the most suitable animals for study. Herein we review the use of nonhuman primates for studies on endometriosis. Objective: To describe the use of nonhuman primates for studies on endometriosis. Methods: We reviewed the literature comparing the use of primate models. Results: In practice, three types of “primate” models exist; 1) studies on monkeys with spontaneous endometriosis; 2) induction of endometriosis in disease-free animals; and, 3) the engraftment of primate tissue into immunodeficient rodents. The absence of tests to identify animals with the wellcharacterized disease greatly limits the viability of studies on spontaneous endometriosis in nonhuman primates. Despite this limitation, studies of spontaneous endometriosis have elucidated risk factors associated with the etiology and pathobiology of the disease. Induced endometriosis in the baboon and macaque currently represents the prototypic and most promising primate model, producing lesions that are phenotypically similar to endometriosis in women, with a well-controlled onset, and predictable pathogenesis. The strength of using induced endometriosis models in nonhuman primates lies in the ability to document the early disease process and the exact age of lesions in the animals. However, nonhuman primates are expensive and in short supply. Xenografts of primate tissue in immunodeficient mice also allow the study of the early disease process but long-term studies are a compromise because of the immunodeficient nature of the host animals. Studies of endometriosis in rhesus and cynomolgus macaques provides an additional benefit as these are the preferred primate models for pharmacokinetic and pharmacodynamic studies in many research institutes and the pharmaceutical industry. Conclusion: Due to the physiological similarities among primates, preclinical studies of endometriosis diagnostics and therapeutics conducted in nonhuman primate models are well-positioned to lead to new clinical applications.