Animal Models in Endometriosis Part-1: Nonhuman Primate Models

摘要

Background: Endometriosis is a painful disorder in women where endometrium-liketissue exists outside of the uterine cavity. Progress on new therapies for the disorder is dependent onphysiologically relevant models. Menstruation and development of spontaneous endometriosis onlyoccur in women and Old World nonhuman primates making nonhuman primates the most suitableanimals 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 spontaneousendometriosis; 2) induction of endometriosis in disease-free animals; and, 3) the engraftment ofprimate tissue into immunodeficient rodents. The absence of tests to identify animals with the wellcharacterizeddisease greatly limits the viability of studies on spontaneous endometriosis in nonhumanprimates. Despite this limitation, studies of spontaneous endometriosis have elucidated riskfactors associated with the etiology and pathobiology of the disease. Induced endometriosis in thebaboon and macaque currently represents the prototypic and most promising primate model, producinglesions that are phenotypically similar to endometriosis in women, with a well-controlledonset, and predictable pathogenesis. The strength of using induced endometriosis models innonhuman primates lies in the ability to document the early disease process and the exact age oflesions in the animals. However, nonhuman primates are expensive and in short supply. Xenograftsof primate tissue in immunodeficient mice also allow the study of the early disease process butlong-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 asthese are the preferred primate models for pharmacokinetic and pharmacodynamic studies in manyresearch institutes and the pharmaceutical industry.Conclusion: Due to the physiological similarities among primates, preclinical studies of endometriosisdiagnostics and therapeutics conducted in nonhuman primate models are well-positioned tolead to new clinical applications.