Gebril Mona, Mulder Sparhawk, Das Rimi, Nallasamy Shanmugasundaram
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
Division of Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, 05405, USA.
Histochem Cell Biol. 2025 Aug 28;163(1):84. doi: 10.1007/s00418-025-02411-3.
Extracellular matrix reorganization, a concurrent process of endometrial decidualization, has garnered widespread recognition. However, our understanding of this process remains limited. In this study, we aimed to investigate the expression, spatial distribution, and reorganization of fibrillar collagens, elastin, and lysyl oxidases within the decidua. Using second harmonic generation imaging, we successfully recorded fibrillar collagen reorganization between preimplantation and decidualized endometrium. Upon embryo implantation, the fibrillar collagens align themselves parallel to the direction of embryo invasion. Furthermore, we employed confocal imaging analysis to reveal distinct expression and spatial distribution patterns of elastin and lysyl oxidase-like enzymes. Elastin expression begins to manifest surrounding the implanting embryo, extends into the decidua, and exhibits a high concentration in the mesometrial region after gestational day 8. All lysyl oxidase-like enzymes are localized within the decidua, although they exhibit varying expression patterns. To gain further insights, we utilized an in vitro stromal cell decidualization model and provided compelling evidence that stromal cells serve as the primary source of the extracellular matrix components during endometrial decidualization. Additionally, we demonstrated that the genes encoding factors involved in the synthesis, processing, and assembly of fibrillar collagen and elastic fibers exhibit differential expression patterns during in vitro decidualization. Genes such as asporin, decorin, thrombospondin 2, fibulin 2, fibulin 5, and lysyl oxidase show significant induction during in vitro decidualization. In summary, our comprehensive analysis provides a detailed evaluation of the expression, spatial distribution, and reorganization of fibrillar collagens, elastin, and lysyl oxidases during the process of endometrial decidualization.
细胞外基质重组是子宫内膜蜕膜化的一个并行过程,已得到广泛认可。然而,我们对这一过程的理解仍然有限。在本研究中,我们旨在研究蜕膜中纤维状胶原蛋白、弹性蛋白和赖氨酰氧化酶的表达、空间分布和重组情况。利用二次谐波产生成像技术,我们成功记录了植入前和蜕膜化子宫内膜之间的纤维状胶原蛋白重组。胚胎植入时,纤维状胶原蛋白会沿胚胎侵入方向平行排列。此外,我们采用共聚焦成像分析来揭示弹性蛋白和赖氨酰氧化酶样酶的独特表达和空间分布模式。弹性蛋白的表达在植入胚胎周围开始显现,延伸至蜕膜,并在妊娠第8天后在子宫系膜区域呈现高浓度。所有赖氨酰氧化酶样酶都定位于蜕膜内,尽管它们表现出不同的表达模式。为了进一步深入了解,我们利用体外基质细胞蜕膜化模型,并提供了有力证据表明基质细胞是子宫内膜蜕膜化过程中细胞外基质成分的主要来源。此外,我们证明了编码参与纤维状胶原蛋白和弹性纤维合成、加工和组装的因子的基因在体外蜕膜化过程中表现出不同的表达模式。诸如抑瘤素、核心蛋白聚糖、血小板反应蛋白2、纤连蛋白2、纤连蛋白5和赖氨酰氧化酶等基因在体外蜕膜化过程中显示出显著诱导。总之,我们的综合分析对子宫内膜蜕膜化过程中纤维状胶原蛋白、弹性蛋白和赖氨酰氧化酶的表达、空间分布和重组进行了详细评估。