The development of a preclinical swine model for endometriosis†

Endometriosis is a benign gynecological condition in which endometrial-like tissue grows outside of the uterus, and the mechanisms of its pathogenesis are not fully understood. The anatomical and physiological parallels between pigs and humans have made pigs a good model for investigating other human diseases. Here, we report on the development of a swine model for endometriosis in which the peritoneal cavity was inoculated with autologous endometrial tissue fragments labeled with fluorescein isothiocyanate (FITC) dye-doped silica nanoparticles. After 6 weeks of endometriosis induction, FITC positive endometriotic lesions were observed on the peritoneal surface of the abdominal wall as well as on the serosal surfaces of the uterus and small intestine. Histological analysis of the endometriotic lesions revealed endometrial-like epithelial and stromal cells that were morphologically comparable to human endometriotic lesions. The identification of epithelial and stromal cells in these lesions was confirmed by immunostaining of e-cadherin, an endometrial epithelial marker, and Chicken ovalbumin upstream promoter-transcription factor II, an endometrial stromal marker. Our results illustrate successful induction of endometriosis with fluorescent-labeled endometriotic lesions to identify in situ endometriotic lesions. According to the size and physiological similarity of pigs to humans, this is an important first step toward the development of a non-invasive tool to diagnose endometriosis. Furthermore, the availability of a new large animal model for translational endometriosis research provides a novel preclinical animal model for laparoscopic monitoring and retrieval of experimental endometriotic lesions with ample serum for serial analyses.