Tissue remodeling of human endometrium occurs during the menstrual cycle to prepare for embryo adhesion and invasion. The ovarian steroid hormones 17β-estradiol and progesterone control the menstrual cycle to achieve the receptive state during the “window of implantation” (WOI). Here, we focus on the human endometrial epithelium and its changes in polarity, adhesion, cytoskeletal organization and the underlying extracellular matrix enabling embryo implantation. The adhesion and invasion of the trophoblast via the apical plasma membrane of epithelial cells is a unique cell biological process, which is coupled to partial epithelial–mesenchymal transition (EMT). Given the fundamental species differences during implantation, we restrict the review mainly to the human situation and focus on cell culture systems to study the interaction between human trophoblast and endometrial cells. We summarize current knowledge based on the relatively scarce in vivo data and the steadily growing in vitro observations using various cell culture systems.

The endometrial epithelium and underlying stroma undergo profound changes to support and limit embryo adhesion and invasion, which occur in the secretory phase of the menstrual cycle during the window of implantation. This coincides with a peak in progesterone and estradiol production. We hypothesized that the interplay between hormone-induced changes in the mechanical properties of the endometrial epithelium and stroma supports this process. To study it, we used hormone-responsive endometrial adenocarcinoma-derived Ishikawa cells growing on substrates of different stiffness. We showed that Ishikawa monolayers on soft substrates are more tightly clustered and uniform than on stiff substrates. Probing for mechanical alterations, we found accelerated stress–relaxation after apical nanoindentation in hormone-stimulated monolayers on stiff substrates. Traction force microscopy furthermore revealed an increased number of foci with high traction in the presence of estradiol and progesterone on soft substrates. The detection of single cells and small cell clusters positive for the intermediate filament protein vimentin and the progesterone receptor further underscored monolayer heterogeneity. Finally, adhesion assays with trophoblast-derived AC-1M-88 spheroids were used to examine the effects of substrate stiffness and steroid hormones on endometrial receptivity. We conclude that the extracellular matrix and hormones act together to determine mechanical properties and, ultimately, embryo implantation.

Dermal fibroblasts are a heterogeneous population consisting of several subpopulations that differ in their origin, anatomical regional specificity, and lo

Preparation for embryo implantation is a complex process that includes changes at both the cellular and tissue levels in the epithelium and stroma of the endometrium of the uterus. The success of pregnancy depends on the regulation of preimplantation changes in the endometrium and the onset of the receptivity period. Modeling the regulation of the functioning of the endometrium in vitro allows us to study the process of preparing the endometrium for embryo implantation, which is especially important for the development of therapeutic approaches for the treatment of diseases associated with infertility. The paper shows the effect of steroid sex hormones on the change in the polarity of the endometrial epithelium in vitro, which is also an important process during implantation in vivo. We also describe the mutual influence of estrogen and progesterone as the main regulators of endometrial functioning on the expression of their receptors.

Mammalian embryonic development includes preimplantation, implantation and post-implantation development, during which the embryo is attached to the uterus wall. The modeling of embryo development in culture allows to study the process of ontogenesis in its dynamic development, which is especially valuable for studying early post-implantation development. We reviewed existing cultivation systems for mouse and human embryos. Also we considered a new experimental approach for studying early mammalian embryogenesis—embryo-like cell constructs. Using these methods, the most important results were obtained about the formation of embryonic germ layers, which provided insights into the molecular and cellular mechanisms of morphogenesis of the mouse and human embryos. The purpose of this review is to generalize the possibilities and limitations of such systems for studying mammalian embryogenesis and to find directions for further development of this approach.