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黏附、附着和侵袭标志物在正常和异位子宫内膜中的表达:与子宫内膜异位症病因的关联。

Expression of adhesion, attachment and invasion markers in eutopic and ectopic endometrium: a link to the aetiology of endometriosis.

机构信息

Division of Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet/Karolinska University Hospital, SE-171 76 Stockholm, Sweden.

出版信息

Hum Reprod. 2012 Sep;27(9):2737-46. doi: 10.1093/humrep/des220. Epub 2012 Jul 4.

DOI:10.1093/humrep/des220
PMID:22767451
Abstract

BACKGROUND

Cell properties, such as attachment, adhesion and invasion, are important for the normal function of the endometrium. However, it is believed that the same properties may also be involved in the development of gynaecological diseases, such as endometriosis. Endometrial cells, shed by retrograde menstruation, may have an aberrant expression of molecules involved in these functions, leading to endometriosis. Therefore, the aim of this study was to investigate the expression of proteins involved in adhesion, attachment and invasion in eutopic and ectopic endometrium.

METHODS

Endometrial biopsy specimens were collected from healthy volunteers (controls: proliferative phase, n = 10; secretory phase, n = 15) and from endometriosis patients (proliferative phase: n = 9, secretory phase: n = 10). Biopsy specimens from endometriomas were also collected (proliferative phase: n = 9, secretory phase: n = 10). Expression of apolipoprotein E (ApoE), integrin β-2 (ITGB2), integrin β-7 (ITGB7), Laminin γ-1 (LAMC1), CD24 molecule (CD24) and junctional adhesion molecule-1 (JAM-1) was evaluated with real-time reverse transcriptase polymerase chain reaction and immunohistochemistry.

RESULTS

The endometrium from controls and women with endometriosis expressed ApoE, ITGB2, ITGB7, LAMC1, CD24 and JAM-1. Gene expression of ApoE and JAM-1 was decreased in both proliferative and secretory phase in the endometrium from women with endometriosis compared with control endometrium. Also, mRNA expression of LAMC1 was reduced in the endometrium from endometriosis patients compared with controls in the proliferative phase. An altered gene expression of CD24 was seen between the endometrium from endometriosis patients and endometriomas in the secretory phase. The ITGB2 protein expression was altered in epithelia cells between the endometrium from healthy volunteers and endometriosis patients in the secretory phase.

CONCLUSIONS

We have shown differential expression of adhesion, attachment and invasion proteins in proliferative and secretory endometrium from controls and endometriosis patients and in endometriomas. This study suggests that molecules with these properties may have a role in the anchoring of endometrial cells at ectopic sites, thus initiating the development of endometriosis.

摘要

背景

细胞的特性,如黏附、黏着和侵袭,对于子宫内膜的正常功能非常重要。然而,人们认为这些特性也可能与妇科疾病的发生有关,如子宫内膜异位症。逆行月经导致的子宫内膜细胞可能会异常表达参与这些功能的分子,从而导致子宫内膜异位症的发生。因此,本研究旨在研究黏附、黏着和侵袭相关蛋白在正常子宫内膜和异位子宫内膜中的表达。

方法

收集健康志愿者(对照组:增生期 n = 10;分泌期 n = 15)和子宫内膜异位症患者(增生期 n = 9,分泌期 n = 10)的子宫内膜活检标本。还收集了子宫内膜异位瘤的活检标本(增生期 n = 9,分泌期 n = 10)。采用实时逆转录聚合酶链反应和免疫组织化学方法评估载脂蛋白 E(ApoE)、整合素 β-2(ITGB2)、整合素 β-7(ITGB7)、层粘连蛋白 γ-1(LAMC1)、CD24 分子(CD24)和连接黏附分子-1(JAM-1)的表达。

结果

对照组和子宫内膜异位症患者的子宫内膜均表达 ApoE、ITGB2、ITGB7、LAMC1、CD24 和 JAM-1。与对照组相比,子宫内膜异位症患者的子宫内膜在增生期和分泌期的 ApoE 和 JAM-1 基因表达均降低。此外,与对照组相比,子宫内膜异位症患者的子宫内膜在增生期 LAMC1 的 mRNA 表达减少。在分泌期,子宫内膜异位症患者的子宫内膜中 CD24 的基因表达发生改变,而子宫内膜异位瘤中 CD24 的基因表达与子宫内膜异位症患者不同。在分泌期,健康志愿者和子宫内膜异位症患者的子宫内膜中上皮细胞的 ITGB2 蛋白表达发生改变。

结论

我们已经证明了在对照组和子宫内膜异位症患者的增生期和分泌期子宫内膜以及子宫内膜异位瘤中,黏附、黏着和侵袭相关蛋白的表达存在差异。本研究表明,具有这些特性的分子可能在子宫内膜细胞在异位部位的锚定中起作用,从而引发子宫内膜异位症的发生。

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