In vivo analysis of menstrual and non-menstrual tissue in murine endometriosis models

Endometriosis is a common gynecological disorder where endometrial tissue grows outside the uterine cavity, causing pain, dysmenorrhea, and infertility. Current treatments, including pain management, ovarian suppression, and surgery, often have high recurrence rates and side effects. Effective therapies with fewer side effects are urgently needed, making animal models crucial for research. Mouse models are increasingly used due to their low cost and genetic modification potential. However, since mice do not menstruate, endometriosis must be experimentally induced by transplanting uterine tissue. A novel model using syngeneic menstrual tissue has been developed to better replicate human endometriosis, but its comparison with non-menstrual tissue under controlled conditions has not been fully explored. This study compared the development of endometriotic lesions from menstrual and non-menstrual tissue fragments under identical experimental conditions. Tissue was transplanted into the peritoneal cavity and dorsal skinfold chambers of non-ovariectomized (non-ovx), ovariectomized (ovx), and ovariectomized with estrogen substitution (ovx+E2) mice. Lesion growth and vascularization were assessed using ultrasound, fluorescence microscopy, histology, and immunohistochemistry. In non-ovx mice, both tissue types showed similar growth. However, in ovx and ovx+E2 mice, lesions from menstrual tissue had slower growth and lower microvessel density compared to non-menstrual tissue. Menstrual tissue grafts also showed delayed vascularization and reduced blood perfusion. This is the first study to compare menstrual and non-menstrual tissue in the development of endometriosis in mice. The findings highlight key differences in growth and vascularization under hormonal manipulation, suggesting that both tissue types are viable models, but the choice should be tailored to specific research goals.