A novel model for endometriosis

Abstract

Human uterine endometrium has unique properties to regenerate and remodel cyclically throughout the woman's reproductive life and also gives rise to endometriosis through ectopic implantation of retrograde shedding including endometrial cells during menstruation. Endometriosis is a common and significant gynecological disorder which can lead to infertility or a certain type of ovarian cancer. However, the etiology and pathogenesis still remain uncertain. Previously, we have reported that singly dispersed cells isolated directly from human endometrium can reconstruct the functional ectopic endometria when transplanted beneath the kidney capsule of the NOD/SCID/γcnull immunodeficient mouse. In addition to the endometrium-like structure, hormone-dependent changes (e.g. proliferation, differentiation, tissue breakdown and shedding) characteristic of cycling human endometrium can be reproduced in the endometrial reconstruct whose blood is supplied by human-mouse chimeric vessels. These results indicate that singly dispersed endometrial cells have potential applications for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation, providing implications for model mechanisms underlying the establishment of endometriotic lesions and the physiological endometrial regeneration during the menstrual cycle. Furthermore, the hormone-dependent behavior of the endometrium reconstructed from lentivirally-engineered endometrial cells expressing a variant luciferase can be assessed noninvasively and quantitatively by in vivo bioluminescence imaging. Our animal model will provide a powerful tool to investigate the pathophysiology of endometriosis and also to validate the effect of novel therapeutic agents and gene targeting on endometriosis with the noninvasive and real-time evaluation system. This animal system can be applied as a unique model for other various types of neoplastic diseases when the relevant cells are transplanted under the kidney capsule. This article describes our novel mouse model and in vivo imaging system with overviews of experimental models for endometriosis.