Extracellular Matrix Reorganization During Endometrial Decidualization

ABSTRACT 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 gestation 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. Summary Sentence Fibrillar collagen, elastic fibers, and lysyl oxidases, synthesized by endometrial stromal cells, exhibit distinct spatial distributions and reorganization patterns within the decidua during embryo implantation. Competing Interest Statement The authors have declared no competing interest. Footnotes Grant support: Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD111479 (SN). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.