FEMALE REPRODUCTIVE TRACT - B
Wednesday, August 4, 2004
10:30 AM–12:30 PM
(817) AN EXPERIMENTAL IN VIVO MODEL FOR PERITONEAL ENDOMETRIOSIS TO DEVELOP THERAPEUTICAL STRATEGIES INTERFERING WITH ANGIOGENESIS AND ESTROGEN METABOLISM.
Gruemmer, Ruth1, Fechner, Sabine1, Schwarzer, Frauke1, Absenger, Yvonne1, Schmidt, Markus2, Winterhager, Elke1, 1 University Hospital Essen, Essen, Germany2 University Hospital Essen, Essen, Germany
ABSTRACT- Endometriosis is characterized by the presence of endometrial tissue at ectopic sites outside the uterus. The disease is associated with dysmenorrhea, pelvic pain and infertility, and its current therapeutical treatment is still associated with a high recurrency rate. The cell biological mechanisms leading to the establishment of endometriosis are yet not understood. To evaluate new therapeutic strategies, fragments of human endometrium from premenopausal women were implanted into the peritoneal cavity of athymic mice. At different time points from 2 to 28 days after transplantation parameters like morphology, proliferation, angiogenesis, differentiation markers, steroid hormone receptors and estrogen converting enzymes were investigated in the ectopic endometrial lesions. Adhesion of endometrial fragments to the peritoneum was observed from day 2 onwards. The lesions persisted up to 28 days revealing a well preserved morphology maintaining proliferation markers and cytokeratin expression in the glandular epithelium. Estrogen receptor and progesterone receptors isoforms as well as the estrone sulfatase gene were present in the cultured endometrium up to 28 days, whereas expression of the estradiol metabolizing enzymes 17beta-hydroxy steroid dehydrogenase(HSD)-1 and 17beta-HSD-2 decreased from day 7 of culturing onwards. Angiogenesis into the endometrial fragments occurred from day 4 after transplantation onwards, and an increase in transcripts of VEGF as well as bFGF and their receptors could be observed in the human tissue during culture in nude mice corresponding to the expression in endometriotic lesions in patients. Thus we could show that culture of human endometrial tissues in the peritoneal cavity of nude mice seems to be a useful experimental model to test compounds interacting with hormonal regulation or angiogenesis to develop new therapeutic concepts in endometriosis.
KEY WORDS: angiogenesis, endometriosis, estrogen metabolism