Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations.
Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations.
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DOI：
10.1242/dmm.049070
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发表时间：
2021-08-01
影响因子：
4.3
通讯作者：
Greaves E
中科院分区：
文献类型：
--
作者：
Dorning A;Dhami P;Panir K;Hogg C;Park E;Ferguson GD;Hargrove D;Karras J;Horne AW;Greaves E
我们对子宫内膜异位症的病因学和病理生理学的了解仍然有限。该领域的疾病建模是有问题的，因为存在许多版本的子宫内膜异位症诱导小鼠模型。我们整合了使用表达端粒酶的供体小鼠产生的“病变”的生物发光成像。我们比较了病变的纵向生物发光和组织学，诱导子宫内膜异位症小鼠的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。检测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病变慢性程度的关键决定因素，以及它们的细胞组成。疼痛样行为的严重程度也因模型而异。尽管西曲瑞克在所有模型中均显著降低了病变生物发光，但其对疼痛样行为的影响不同。总的来说，我们的研究结果表明，在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在女性中观察到的不同亚型/异质性，应该成为子宫内膜异位症领域发现科学的标准方法。总结：诱导子宫内膜异位症的同基因小鼠模型的不同版本表现出病变的慢性和细胞组成的差异，以及与子宫内膜异位症相关的痛觉过敏。
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. Summary: Different versions of syngeneic mouse models of induced endometriosis exhibit disparities in chronicity and cellular composition of lesions, as well as endometriosis-associated hyperalgesia.
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影响因子：
3.7
作者：
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通讯作者：
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