The ischemic time window of ectopic endometrial tissue crucially determines its ability to develop into endometriotic lesions

Abstract

Endometriosis develop from shed endometrial fragments via retrograde menstruation. This affects the survival, proliferation and vascularization of the tissue and its final ability to form endometriotic lesions. Within this study, uterine tissue samples from donor mice were precultivated for 24 h or 72 h to simulate avascular periods. Their morphology, microvessel density, apoptotic activity and expression of angiogenesis-related proteins were analyzed in vitro. The formation of endometriotic lesions in vivo was assessed after transplantation of precultivated uterine tissue samples to the abdominal wall and dorsal skinfold chambers by means of high-resolution ultrasound, intravital fluorescence microscopy, histology and immunohistochemistry. In vitro, 72-h-precultivated uterine tissue samples exhibit extensive areas of tissue necrosis and high numbers of apoptotic cells as well as a significantly reduced cell and microvessel density. These samples failed to develop into endometriotic lesions. In contrast, the 24-h-precultivated samples showed, that their early vascularization and growth in vivo was improved when compared to controls. This indicates that avascular periods have a strong impact on the survival of ectopic endometrial tissue and the chance for the development of endometriosis.