Abstract
ABSTRACTOur understanding of the aetiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of ‘lesions’ generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behaviour of mice with induced endometriosis and the impact of the gonadotropin-releasing hormone antagonist Cetrorelix on lesion regression and sensory behaviour. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were, as well as their cellular composition. The severity of pain-like behaviour also varied across models. Although Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behaviour. Collectively, our results demonstrate key differences in the progression of the ‘disease’ across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes/heterogeneity observed in women, should become a standard approach to discovery science in the field of endometriosis.
Highlights
Endometriosis is an enigmatic, incurable condition impacting 190 million women worldwide during their reproductive years
We previously developed a mouse model of induced endometriosis that aims to recapitulate the process of retrograde menstruation; endometrial breakdown is induced in a ‘menses’-like event(Cousins et al, 2014) in a donor mouse and the resulting ‘menstrual’ tissue is injected into the peritoneal cavity of ovariectomized recipient mice supplemented with estradiol
Several other variations of endometriosis mouse models exist that vary in the nature of uterine material introduced into the peritoneal cavity
Summary
Endometriosis is an enigmatic, incurable condition impacting 190 million women worldwide during their reproductive years. Careful re-appraisals of the pathology of endometriosis highlight the variable nature of their components and suggest that typical endometriosis should contain endometroid epithelium, or stroma, or fibrosis or hemosiderin-laden macrophages. These often co-occur but not in all instances(Clement, 2007, Vigano et al, 2018). One of the most widely accepted theories for the development of endometriosis is dissemination of endometrial fragments resulting from retrograde menstruation(Sampson, 1927) It remains unknown why endometriosis occurs in a proportion of women when approximately 90% of women experience retrograde menstruation. Heterogeneity in disease severity and lesion subtypes (superficial peritoneal, ovarian endometrioma and deep infiltrating) suggest that endometriosis could have multiple origins and other theories are increasingly being discussed(Sourial et al, 2014)
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