Medical Research Council Centre for Reproductive Health, Queen's Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK.
Centre for Early Life, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Dis Model Mech. 2021 Aug 1;14(8). doi: 10.1242/dmm.049070. Epub 2021 Aug 31.
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.
我们对子宫内膜异位症的病因和病理生理学的理解仍然有限。该领域的疾病建模存在问题,因为存在许多诱导的子宫内膜异位症小鼠模型版本。我们整合了使用荧光素酶表达供体小鼠生成的“病变”的生物发光成像。我们比较了诱导子宫内膜异位症小鼠的病变的纵向生物发光和组织学、感觉行为以及促性腺激素释放激素拮抗剂 Cetrorelix 对病变消退和感觉行为的影响。测试了四种子宫内膜异位症模型。我们发现供体子宫材料的性质是决定病变慢性程度以及其细胞组成的关键因素。类似疼痛行为的严重程度也因模型而异。尽管 Cetrorelix 显著降低了所有模型中的病变生物发光,但对类似疼痛行为的影响却有所不同。总的来说,我们的结果表明,不同的子宫内膜异位症小鼠模型中“疾病”的进展存在关键差异。我们建议,在多个模型中进行验证和测试,每个模型都可能代表女性中观察到的不同亚型/异质性,这应该成为子宫内膜异位症领域发现科学的标准方法。