Hwang Jung Hye, Park Moon Il, Hwang Youn Young, Yoo Hyung Jin, Mardon Helen J
Department of Obstetrics and Gynecology, College of Medicine, Hanyang University, Seoul, Korea.
Exp Mol Med. 2002 Jul 31;34(3):194-200. doi: 10.1038/emm.2002.28.
Integrins are heterodimeric glycoproteins that have been found to undergo dynamic temporal and spatial changes in the endometrium during the menstrual cycle and in early pregnancy. Specificity of integrins is known to be different in human endometrial stromal cells and decidual cells. These shifts of integrins suggested to play an important role in embryo implantation and can be modulated by progesterone, cAMP derivatives, and cytokines. The mechanisms of decidualization and its precise physiological role are still not clearly understood and in vitro systems could provide an alternative that overcomes limitations of studying such complex biological phenomena in vivo at the time of implantation. This study was undertaken to establish an in vitro model system for human decidualization using 8-bromo-cAMP and to investigate the characteristics of stromal integrin expression in vitro by 8-Br-cAMP. Endometrial stromal cells were isolated and cultured, and then were induced to decidualize by 0.5 mM 8-Br-cAMP for 15 days. Immunofluorescence staining and flow cytometric analyses of the integrin subunits (alpha1, alpha4, alpha5, alpha6, beta1 and alphavbeta3) were performed at day 9. In the presence of 8-Br-cAMP, the staining intensity of alphavbeta3 was significantly higher than control and measurements for alpha1, alpha4, alpha5, alpha6, and beta1 were similar. Immunofluorescent localization of the integrins reflected the differences obtained from the flow cytometric analyses described above. In summary, the expression of alphavbeta3 integrin increased in stromal cells in vitro decidualized by 8-Br-cAMP and this up-regulation of alphavbeta3 integrin expression during decidualization might influence on human implantation.
整合素是异二聚体糖蛋白，已发现在月经周期和早孕期间子宫内膜会发生动态的时空变化。已知整合素在人子宫内膜基质细胞和蜕膜细胞中的特异性不同。整合素的这些变化提示在胚胎着床中起重要作用，并且可受到孕酮、环磷酸腺苷衍生物和细胞因子的调节。蜕膜化的机制及其确切的生理作用仍未完全清楚，体外系统可提供一种替代方法，克服在着床时体内研究此类复杂生物学现象的局限性。本研究旨在建立一种使用8-溴环磷酸腺苷进行人蜕膜化的体外模型系统，并通过8-溴环磷酸腺苷研究体外基质整合素表达的特征。分离并培养子宫内膜基质细胞，然后用0.5 mM 8-溴环磷酸腺苷诱导蜕膜化15天。在第9天对整合素亚基（α1、α4、α5、α6、β1和αvβ3）进行免疫荧光染色和流式细胞术分析。在8-溴环磷酸腺苷存在下，αvβ3的染色强度明显高于对照组，而α1、α4、α5、α6和β1的测量结果相似。整合素的免疫荧光定位反映了上述流式细胞术分析获得的差异。总之，8-溴环磷酸腺苷体外诱导蜕膜化的基质细胞中αvβ3整合素表达增加，蜕膜化过程中αvβ3整合素表达的这种上调可能影响人类着床。
