Tubal origin of ovarian endometriosis
Tubal origin of ovarian endometriosis
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卵巢子宫内膜异位症的输卵管起源
DOI：
10.1038/modpathol.2013.245
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发表时间：
2014-08-01
期刊：
影响因子：
7.5
通讯作者：
Zheng, Wenxin
中科院分区：
文献类型：
--
作者：
Yuan, Zeng;Wang, Lijie;Zheng, Wenxin
子宫内膜异位症是一种令人困惑和衰弱的疾病，影响世界各地数百万妇女。卵巢是子宫内膜异位症最常见的器官部位。尽管关于其起源的细胞有各种各样的假设，但仍然存在不确定性。根据我们的临床病理观察，我们推测输卵管可能有助于卵巢子宫内膜异位症的组织发生。为了检验卵巢子宫内膜异位症输卵管起源的假说是否有科学证据支持，我们通过基因差异阵列研究鉴定了一组在正常输卵管或子宫内膜中高表达的新基因。在众多的差异表达基因中，选择FMO3和DMBT1作为初始生物标志物来验证这一假设。然后，通过实时PCR、蛋白质印迹和免疫组织化学分析比较这些生物标志物在相同患者输卵管和子宫内膜中的表达水平，在具有子宫内膜异位病灶的卵巢切片中验证这些生物标志物。FMO3在输卵管上皮中呈高表达，在配对的子宫内膜中呈低表达。相反，DMBT1在子宫内膜中高，但在输卵管中低。在32例卵巢子宫内膜异位症患者中，18例（56%）FMO3高表达，DMBT1低表达。然而，14例（44%）子宫内膜异位症病例显示这两种标记物的表达模式相反。蛋白质印迹和免疫组织化学方法的结果相似。结果表明，我们研究的卵巢子宫内膜异位症中约60%可能来自输卵管，而约40%的病例可能来自子宫内膜。输卵管上皮可能是卵巢子宫内膜异位症的组织来源之一。这些需要确认的新发现可能对寻找预防和治疗子宫内膜异位症的替代方法产生重大临床影响。
Endometriosis is a puzzling and debilitating disease that affects millions of women around the world. Ovary is the most common organ site involved by endometriosis. Despite various hypotheses about its cell of origin, uncertainty remains. On the basis of our clinicopathologic observations, we hypothesize that fallopian tube may contribute the histogenesis of ovarian endometriosis. To examine if the hypothesis, tubal origin of ovarian endometriosis, has scientific supporting evidence, we identified a set of novel genes, which are either highly expressed in the normal fallopian tube or in the endometrium through a gene differential array study. Among many differentially expressed genes, FMO3 and DMBT1 were selected as the initial biomarkers to test the hypothesis. These biomarkers were then validated in ovarian sections with foci of endometriosis by comparing their expression levels in the fallopian tube and the endometrium within the same patients with real-time PCR, western blot and immunohistochemistry analysis. FMO3 was highly expressed in the tubal epithelia while low in the paired endometrium. In contrast, DMBT1 was high in the endometrium but low in the fallopian tube. In 32 ovarian endometriosis cases analyzed by real-time PCR, 18 (56%) showed a high level of FMO3 and a low level of DMBT1 expression. However, 14 (44%) endometriosis cases showed a reversed expression pattern with these two markers. Results were similarly seen in the methods of western blot and immunohistochemistry. The findings suggest that approximately 60% of the ovarian endometriosis we studied may be derived from the fallopian tube, whereas about 40% of the cases may be of endometrial origin. The fallopian tube epithelia may represent one of the tissue sources contributing to ovarian endometriosis. Such novel findings, which require confirmation, may have a significant clinical impact in searching for alternative ways of prevention and treatment of endometriosis.