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蜕膜化减弱在位和异位子宫内膜基质细胞的收缩性:对子宫内膜异位症激素治疗的意义。

Decidualization attenuates the contractility of eutopic and ectopic endometrial stromal cells: implications for hormone therapy of endometriosis.

作者信息

Tsuno Akitoshi, Nasu Kaei, Yuge Akitoshi, Matsumoto Harunobu, Nishida Masakazu, Narahara Hisashi

机构信息

Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Idaigaoka 1-1, Hasama-machi, Yufu-shi, Oita 879-5593, Japan.

出版信息

J Clin Endocrinol Metab. 2009 Jul;94(7):2516-23. doi: 10.1210/jc.2009-0207. Epub 2009 Apr 7.

Abstract

CONTEXT

Decidualization of the endometrium involves the morphological and biochemical reprogramming of the estrogen-primed proliferative endometrial stromal compartment under the continuing influence of progesterone.

OBJECTIVES

The aim of this study was to evaluate the involvement of the extracellular matrix contractility of eutopic and ectopic endometrial stromal cells during the tissue remodeling processes associated with decidualization.

DESIGN

The effect of decidualization on the contractile profile of the endometriotic cyst stromal cells and eutopic endometrial stromal cells with or without endometriosis in the three-dimensional collagen gel culture was investigated using laser scanning microscopy, collagen gel contraction assays, and Western blot analysis.

RESULTS

Decidualized ectopic and eutopic endometrial stromal cells in the three-dimensional collagen gel culture mimicked the morphology of decidual tissue in vivo. In vitro decidualization inhibited the contractility of these eutopic and ectopic endometrial stromal cells. Down-regulation of integrin alpha1beta1 and alpha2beta1 expression, suppression of Ras homology A (Rho A), Rho-associated coiled-coil-forming protein kinase (ROCK)-I and ROCK-II expression, inhibition of the differentiation into the myofibroblastic phenotype, and induction of differentiation into epithelioid decidual phenotype were observed in these cells during decidualization.

CONCLUSIONS

It is suggested that the attenuation of eutopic endometrial stromal cell-mediated contractility by decidualization is a novel and integral mechanism of the physiological endometrial tissue remodeling process during menstrual cycles. Although ectopic endometrial stromal cells have enhanced contractile profile, decidualization can attenuate the contractility of these cells. These findings may be one of the action mechanisms by which oral contraceptives and progestins ameliorate endometriosis.

摘要

背景

子宫内膜蜕膜化涉及在孕激素持续影响下,雌激素预处理的增殖期子宫内膜基质细胞的形态和生化重编程。

目的

本研究旨在评估在与蜕膜化相关的组织重塑过程中,在位和异位子宫内膜基质细胞的细胞外基质收缩性的作用。

设计

使用激光扫描显微镜、胶原凝胶收缩试验和蛋白质印迹分析,研究了蜕膜化对三维胶原凝胶培养中子宫内膜异位囊肿基质细胞以及有无子宫内膜异位症的在位子宫内膜基质细胞收缩特性的影响。

结果

三维胶原凝胶培养中的蜕膜化异位和在位子宫内膜基质细胞模拟了体内蜕膜组织的形态。体外蜕膜化抑制了这些在位和异位子宫内膜基质细胞的收缩性。在蜕膜化过程中,这些细胞中观察到整合素α1β1和α2β1表达下调、Ras同源物A(Rho A)、Rho相关卷曲螺旋形成蛋白激酶(ROCK)-I和ROCK-II表达受抑制、向肌成纤维细胞表型分化受到抑制以及向类上皮蜕膜表型分化受到诱导。

结论

提示蜕膜化使在位子宫内膜基质细胞介导的收缩性减弱是月经周期中生理性子宫内膜组织重塑过程的一种新的重要机制。尽管异位子宫内膜基质细胞具有增强的收缩特性,但蜕膜化可减弱这些细胞的收缩性。这些发现可能是口服避孕药和孕激素改善子宫内膜异位症的作用机制之一。

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