A mouse model of endometriosis that displays vaginal, colon, cutaneous, and bladder sensory comorbidities
A mouse model of endometriosis that displays vaginal, colon, cutaneous, and bladder sensory comorbidities
复制标题
DOI：
10.1096/fj.202002441r
复制
发表时间：
2021-04-01
期刊：
影响因子：
4.8
通讯作者：
Brierley, Stuart M.
中科院分区：
文献类型：
--
作者：
Castro, Joel;Maddern, Jessica;Brierley, Stuart M.
子宫内膜异位症是一种痛苦的炎症性疾病，大约10%的育龄妇女受到影响。虽然慢性盆腔疼痛（CPP）仍然是子宫内膜异位症患者的主要症状，但缺乏适当的治疗方法。概括子宫内膜异位症女性的特征和症状的动物模型对于研究子宫内膜异位症的病因以及开发新的治疗方法至关重要。在这项研究中，我们使用自体子宫内膜异位症小鼠模型来检查疾病特征和症状的组合，包括：子宫内膜异位症病变发展的10周时间过程；慢性炎症环境和病变内神经血管生成的发展；清醒动物对阴道、结肠、膀胱和皮肤刺激的感觉超敏反应和疼痛反应改变；以及自发的动物行为。我们发现从移植后第6周起病变大小显著增加。病变显示子宫内膜腺，间质，并行神经血管新生。此外，子宫内膜异位症小鼠的腹膜液中含有已知的炎症介质和血管生成因子。与Sham相比，患有子宫内膜异位症的小鼠表现出：对(1)阴道和(2)结肠直肠膨胀引起的疼痛的敏感性增强，(3)膀胱功能改变，对皮肤(4)热刺激和(5)机械刺激的敏感性增加。子宫内膜异位症的发展对自发行为没有影响。本研究描述了子宫内膜异位症小鼠模型的综合特征，概述了子宫内膜异位症女性的临床特征和症状。此外，它为研究子宫内膜异位症的病因提供了基础，并为治疗干预措施的发展提供了平台，以管理子宫内膜异位症相关的CPP。
Endometriosis is a painful inflammatory disorder affecting similar to 10% of women of reproductive age. Although chronic pelvic pain (CPP) remains the main symptom of endometriosis patients, adequate treatments for CPP are lacking. Animal models that recapitulate the features and symptoms experienced by women with endometriosis are essential for investigating the etiology of endometriosis, as well as developing new treatments. In this study, we used an autologous mouse model of endometriosis to examine a combination of disease features and symptoms including: a 10 week time course of endometriotic lesion development; the chronic inflammatory environment and development of neuroangiogenesis within lesions; sensory hypersensitivity and altered pain responses to vaginal, colon, bladder, and skin stimulation in conscious animals; and spontaneous animal behavior. We found significant increases in lesion size from week 6 post-transplant. Lesions displayed endometrial glands, stroma, and underwent neuroangiogenesis. Additionally, peritoneal fluid of mice with endometriosis contained known inflammatory mediators and angiogenic factors. Compared to Sham, mice with endometriosis displayed: enhanced sensitivity to pain evoked by (i) vaginal and (ii) colorectal distension, (iii) altered bladder function and increased sensitivity to cutaneous (iv) thermal and (v) mechanical stimuli. The development of endometriosis had no effect on spontaneous behavior. This study describes a comprehensive characterization of a mouse model of endometriosis, recapitulating the clinical features and symptoms experienced by women with endometriosis. Moreover, it delivers the groundwork to investigate the etiology of endometriosis and provides a platform for the development of therapeutical interventions to manage endometriosis-associated CPP.