An in vivo-model to investigate therapeutical approaches for the treatment of peritoneal endometriosis

Endometriosis is a common gynecologic disorder characterized by the presence of endometrial tissue outside the uterus. The disease is associated with dysmenorrhea, pelvic pain and infertility, but the cell biological mechanisms involved in the pathogenesis are yet not understood. It is known that angiogenesis is a prerequisite for the maintenance of endometriotic lesions and it is discussed that an elevated estrogen concentration within the ectopic lesions may support their persistance. To investigate the role of those parameters for the maintenance of ectopic endometrial lesions, we established an in-vivo-model by transplanting human endometrial tissue into the peritoneal cavity of nude mice. At 2 to 28 days after implantation angiogenesis as well as the expression of steroid hormone receptors and estrogen-converting enzymes were investigated in the endometriotic lesions. Neoangiogenesis of mouse vessels into the human endometrial fragments occurred from day 4 after transplantation onwards. This correlated to an increase in transcripts of VEGF and bFGF as well as of their specific receptors. The lesions revealed a well preserved morphology up to 28 days, expression of differentiation markers, of estrogen receptor alpha, progesterone receptors and of different estrogen converting enzymes. We demonstrated that in this in vivo model the expression of steroid hormone receptors as well as of aromatase was regulated in the human ectopic endometrial lesions by systemic application of gestagen, antigestagen (RU486) and the gonadotropin inhibitor danazol. Thus we could show that culturing of human endometrial tissues in the peritoneal cavity of nude mice is an useful experimental model to evaluate cell biological mechanisms responsible for the persistence of ectopic endometrium in the peritoneal cavity.