A modified baboon model for endometriosis
A modified baboon model for endometriosis
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DOI：
10.1111/j.1749-6632.2002.tb02791.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Bulun, S
中科院分区：
文献类型：
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作者：
Fazleabas, AT;Brudney, A;Bulun, S
子宫内膜异位症是不孕不育和慢性盆腔疼痛的最常见原因之一，在育龄组中每10名妇女中就有1名受到影响。虽然这种疾病的存在已有100多年的历史，但我们目前对其发病机制、相关不孕症的病理生理学以及其自发进化的了解有限。我们缺乏知识有几个原因，最关键的是难以对妇女进行客观的长期研究。因此，我们和其他人已经开发出一种合适的非人类灵长类动物，以研究这种疾病的病因学。我们认为子宫内膜异位症有两个不同的发展阶段。I期是侵袭性的，依赖卵巢类固醇。II期是疾病的活跃期，以内源性雌激素生物合成为特征。在连续两个月经周期接种月经子宫内膜组织后，狒狒会出现与人类相似的病变。术后1个月、4个月和10个月的腹腔镜检查显示，第1个月以红色隆起结节为主，4个月和10个月时均可见红色病变和红蓝色增殖性子宫内膜异位病变。组织学证实这些病变中腺组织和间质成纤维细胞的存在。在1个月和4个月获得的皮损主要表达雌激素受体β(ERbeta)、基质金属蛋白酶-7(MMP-7)和血管内皮生长因子(VEGF)。然而，芳香酶的表达只在10个月时才明显，尽管一些在4个月时获得的皮损表达水平很低。因此，我们的初步数据表明，可以在狒狒体内人工诱导子宫内膜异位症，外源性和内源性雌二醇在增殖、血管生成和免疫调节中的作用现在可以以潜在的系统性方式进行评估。
Endometriosis is one of the most common causes of infertility and chronic pelvic pain and affects 1 in 10 women in the reproductive-age group. Although existence of this disease has been known for over 100 years, our current knowledge of its pathogenesis, the pathophysiology of related infertility, and its spontaneous evolution is limited. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed the baboon as an appropriate nonhuman primate to study the etiology of this disease. We suggested that endometriosis develops in two distinct phases. Phase I is invasive and dependent on ovarian steroids. Phase II, which is the active phase of the disease, is characterized by endogenous estrogen biosynthesis. Following inoculation with menstrual endometrial tissues in two consecutive menstrual cycles, baboons develop lesions that are similar to those seen in humans. Laparoscopy at 1, 4, and 10 months revealed a preponderance of red raised nodules at the first month, while both red lesions and reddish-blue proliferative endometriotic lesions were evident at 4 and 10 months. The presence of glandular tissue and stromal fibroblasts in these lesions was confirmed by histology. Lesions obtained at 1 and 4 months expressed estrogen receptor beta (ERbeta), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor (VEGF) predominantly. However, aromatase expression was only readily evident at 10 months, although some lesions obtained at 4 months expressed low levels of aromatase. Therefore, our preliminary data suggest that endometriosis can be artificially induced in baboons, and the role of exogenous and endogenous estradiol in proliferation, angiogenesis, and immune modulations can now be evaluated in a potentially systemic manner.