A syngeneic inoculation mouse model of endometriosis that develops multiple comorbid visceral and cutaneous pain like behaviours

Abstract

Endometriosis is a chronic and debilitating condition, commonly characterised by chronic pelvic pain (CPP) and infertility. Chronic pelvic pain can be experienced across multiple pelvic organs, with comorbidities commonly effecting the bowel, bladder, and vagina. Despite research efforts into endometriosis pathophysiology, little is known about how endometriosis induces CPP, and as such, therapeutic interventions are lacking. The aim of this study was to characterise a syngeneic mouse model of endometriosis that mimics naturally occurring retrograde menstruation, thought to precede endometriosis development in patients, and determine whether these mice exhibit signs of CPP and altered behaviour. We characterised the development of endometriosis over 10 weeks following uterine tissue inoculation, measured in vivo and ex vivo hypersensitivity to mechanical stimuli across multiple visceral organs, and assessed alterations in animal spontaneous behaviour. We confirmed that inoculated uterine horn tissue formed into endometriosis lesions throughout the peritoneal cavity, with significant growth by 8 to 10 weeks post inoculation. Additionally, we found that mice with fully developed endometriosis displayed hypersensitivity evoked by (1) vaginal distension, (2) colorectal distension, (3) bladder distension, and (4) cutaneous thermal stimulation, compared to their sham counterparts. Moreover, endometriosis mice displayed alterations in spontaneous behaviour indicative of (5) altered bladder function and (6) anxiety. This model creates a foundation for mechanistical studies into the diffuse CPP associated with endometriosis and the development of targeted therapeutic interventions to improve the quality of life of women with endometriosis.