Evaluation of Estrogen Treatment in an Immunodeficient Mouse Endometriosis Model
Evaluation of Estrogen Treatment in an Immunodeficient Mouse Endometriosis Model
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DOI：
10.1159/000240672
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发表时间：
2009-01-01
影响因子：
2.1
通讯作者：
Donnez, Jacques
中科院分区：
文献类型：
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作者：
Colette, Sebastien;Defrere, Sylvie;Donnez, Jacques
背景/目的：子宫内膜异位症是一种雌激素依赖性疾病。然而，只有少数研究分析了雌激素治疗对异种移植人子宫内膜的小鼠的影响。本研究的目的是使以前开发的异源小鼠模型适用于雌激素的研究，并测试雌酮治疗对子宫内膜异位症发展的影响。方法：将人增殖期子宫内膜异种移植于去势免疫缺陷小鼠腹腔内。这些小鼠通过皮下雌酮释放丸用雌激素治疗。21天后评价雌酮对雌二醇水平、子宫组织学和子宫内膜异位症发展的影响。结果：证实了雌酮微丸的生物活性及其代谢产物雌二醇。然而，对子宫内膜异位症的发展没有影响（病变数量、重量、大小或荧光无差异）。这种反应的缺乏不是由于雌激素受体表达的缺乏，因为在所有收集的病变中发现了强表达。令人惊讶的是，去势的未治疗小鼠呈现出显示高增殖活性的病变，与治疗小鼠中发现的病变相似（约30%）。结论：从卵巢切除未治疗小鼠中恢复的病变中观察到的高增殖质疑在异源小鼠模型中使用雌激素的实用性。版权所有（C）2009 S. Karger AG，巴塞尔
Background/Aims: Endometriosis is known to be an estrogen-dependent disease. However, only a few studies have analyzed the effect of estrogen treatment in mice xenotransplanted with human endometrium. The objective of this study was to adapt a previously developed heterologous murine model to the study of estrogens and test the impact of estrone treatment on endometriosis development. Methods: Human proliferative endometrium was xenotransplanted into the peritoneal cavity of castrated immunodeficient mice. These mice were treated with estrogens by means of subcutaneous estrone-releasing pellets. The effect of estrone on estradiol level, uterine histology and endometriosis development was evaluated after 21 days. Results: Bioactivity of estrone pellets and their metabolization into estradiol were demonstrated. However, there was no impact on endometriosis development (no difference in lesion number, weight, size or fluorescence). This lack of response was not due to absence of estrogen receptor expression, since strong expression was found in all lesions harvested. Surprisingly, castrated nontreated mice presented with lesions showing high proliferative activity, similar to lesions found in treated mice (around 30%). Conclusion: The high proliferation observed in lesions recovered from ovariectomized nontreated mice questions the utility of using estrogens in heterologous murine models. Copyright (C) 2009 S. Karger AG, Basel