Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations

Author:

Dorning Ashley1ORCID,Dhami Priya2,Panir Kavita2ORCID,Hogg Chloe1,Park Emma1,Ferguson Gregory D.3,Hargrove Diane3,Karras James3,Horne Andrew W.1ORCID,Greaves Erin2ORCID

Affiliation:

1. Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK

2. Centre for Early Life, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK

3. Ferring Research Institute, 4245 Sorrento Valley Blvd, San Diego, CA 92121, USA

Abstract

ABSTRACT Our 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.

Funder

Ferring Pharmaceuticals

Medical Research Council

Wellbeing of Women

Publisher

The Company of Biologists

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology and Microbiology (miscellaneous),Medicine (miscellaneous),Neuroscience (miscellaneous)

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