Peritoneal endometriosis: validation of an in-vivo model

• Published in: Human reproduction (Oxford) 2001-08, Vol.16 (8), p.1736-1743
• Main Authors: Grümmer, Ruth, Schwarzer, Frauke, Bainczyk, Katja, Hess-Stumpp, Holger, Regidor, Pedro-A., Schindler, Adolf E., Winterhager, Elke
• Format: Article
• Language: English
• Subjects: Adult; angiogenesis; Animals; Biological and medical sciences; Cell Differentiation; Cell Division; Disease Models, Animal; ectopic endometrium; endometriosis; Endometriosis - metabolism; Endometriosis - pathology; Endometrium - transplantation; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Keratins - analysis; Ki-67 Antigen - analysis; Medical sciences; Mice; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Neovascularization, Pathologic; NOD-SCID mouse; Non tumoral diseases; nude mouse; Ovariectomy; Peritoneal Diseases - metabolism; Peritoneal Diseases - pathology; Premenopause; Receptors, Estrogen - analysis; Receptors, Progesterone - analysis; Tissue Adhesions; Vimentin - analysis
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/16.8.1736

BACKGROUND: The current medical treatment of endometriosis, a common gynaecological disease, is still associated with a high recurrence rate. To establish an appropriate in-vivo model to evaluate new therapeutic strategies we validated the nude mouse model for the intraperitoneal cultivation of human endometrial tissue. METHODS: Human endometrium of the proliferative phase was implanted into the peritoneal cavity of normal cycling and ovariectomized athymic mice and of cycling non-obese diabetic (NOD)-severe combined immuno-deficiency (SCID) mice. Morphology, proliferation, differentiation, and angiogenesis in the ectopic endometrium at different time points after implantation was investigated. RESULTS: Adhesion of endometrial fragments was observed from day 2 onwards. The lesions persisted for up to 28 days revealing a well preserved glandular morphology. The glandular epithelium maintained cytokeratin expression even after 14 days of culture. With progressing culture, glands exhibited vimentin staining in combination with a decrease of surrounding stromal cells. Proliferation of glandular epithelium could be demonstrated throughout the investigated period of 28 days, whereas expression of oestrogen and progesterone receptors was maintained only in endometriotic lesions grown in cycling but not in ovariectomized mice. Neoangiogenesis occurred from day 4 onwards, independent from the intraperitoneal localization of the ectopic lesions. CONCLUSIONS: This in-vivo model is a promising tool to test the effect of compounds such as different hormone agonists/antagonists or anti-angiogenic factors to develop new therapeutic concepts in endometriosis.