Department of Molecular and Developmental Medicine, University of Siena, Siena 53100, Italy.
Exosomics SpA, Siena 53100, Italy.
Cells. 2020 Apr 30;9(5):1121. doi: 10.3390/cells9051121.
Embryo implantation has been defined as the "black box" of human reproduction. Most of the knowledge on mechanisms underlining this process derives from animal models, but they cannot always be translated to humans. Therefore, the development of an in vitro/ex vivo model recapitulating as closely and precisely as possible the fundamental functional features of the human endometrial tissue is very much desirable. Here, we have validated endometrial organoids as a suitable 3D-model to studying epithelial endometrial interface for embryo implantation. Transmission and scanning electron microscopy analyses showed that organoids preserve the glandular organization and cell ultrastructural characteristics. They also retain the responsiveness to hormonal treatment specific to the corresponding phase of the menstrual cycle, mimicking the in vivo glandular-like aspect and functions. Noteworthy, organoids mirroring the early secretive phase show the development of pinopodes, large cytoplasmic apical protrusions of the epithelial cells, traditionally considered as reliable key features of the implantation window. Moreover, organoids express glycodelin A (GdA), a cycle-dependent marker of the endometrial receptivity, with its quantitative and qualitative features accounting well for the profile detected in the endometrium in vivo. Accordingly, organoids deriving from the eutopic endometrium of women with endometriosis show a GdA glycosylation pattern significantly different from healthy organoids, confirming our prior data on endometrial tissues. The present results strongly support the idea that organoids may closely recapitulate the molecular and functional characteristics of their cells/tissue of origin.
胚胎着床一直被定义为人类生殖的“黑匣子”。大多数关于这一过程背后机制的知识来源于动物模型，但这些模型并不总是适用于人类。因此，开发一种尽可能精确地再现人类子宫内膜组织基本功能特征的体外/离体模型是非常可取的。在这里，我们验证了子宫内膜类器官是研究胚胎着床时上皮性子宫内膜界面的合适 3D 模型。透射电子显微镜和扫描电子显微镜分析表明，类器官保留了腺体组织和细胞超微结构特征。它们还保留了对特定于月经周期相应阶段的激素治疗的反应性，模拟了体内类似腺体的方面和功能。值得注意的是，模拟早期分泌期的类器官显示出顶端突起的形成，即上皮细胞的大的细胞质顶端突起，传统上被认为是着床窗口的可靠关键特征。此外，类器官表达糖蛋白 A（GdA），这是子宫内膜容受性的周期依赖性标志物，其定量和定性特征与体内子宫内膜中检测到的特征非常吻合。因此，来源于子宫内膜异位症患者的腔内膜的类器官表现出的 GdA 糖基化模式与健康类器官显著不同，这证实了我们之前对子宫内膜组织的研究数据。这些结果强烈支持这样一种观点，即类器官可能紧密地再现其细胞/组织的分子和功能特征。
