Abstract
During decidualization, human mesenchymal-like endometrial stromal cells undergo well characterized cellular and molecular transformations in preparation for accepting a developing embryo. Modulation of cellular biophysical properties during decidualization is likely to be important in receptivity and support of the embryo in the uterus. Here we assess the biophysical properties of human endometrial stromal cells including topography, roughness, adhesiveness and stiffness in cells undergoing in vitro decidualization. A significant reduction in cell stiffness and surface roughness was observed following decidualization. These morphodynamical changes have been shown to be associated with alterations in cellular behavior and homeostasis, suggesting that localized endometrial cell biophysical properties play a role in embryo implantation and pregnancy. This cell–cell communication process is thought to restrict trophoblast invasion beyond the endometrial stroma, be essential in the establishment of pregnancy, and demonstrate the altered endometrial dynamics affecting cell–cell contact and migration regimes at this crucial interface in human reproduction.
Highlights
Decidualization is a biological transformation process that closely resembles a mesenchymal–epithelial transition (MET), occurring independently of the presence of an implanting blastocyst
Elevated progesterone stimulates an increase in the intracellular secondary messenger, cyclic adenosine monophosphate, which sensitizes stromal cells to progesterone through activation of the protein kinase A (PKA) pathway, and subsequent activation of progesterone receptor targets involved in the decidualization process.[8,9,10]
A stabilization of all three indices, which mark the decidualization progression, was obtained approximately after 72 h. decidual PRL (dPRL) and insulin-like growth factor binding protein-1 (IGFBP-1), which are known markers of decidualization, increase in expression in the epithelial and stromal cell region of the endometrium, starting in the secretory phase of the menstrual cycle, and usually increase in the first trimester of pregnancy. dPRL and IGFBP-1 secretion levels were measured throughout the experiment, and were increased significantly after 24 h of exposure to the in vitro decidualization stimulus compared to untreated controls (Figure 2, P b 0.0001), confirming a decidual response
Summary
Decidualization is a biological transformation process that closely resembles a mesenchymal–epithelial transition (MET), occurring independently of the presence of an implanting blastocyst. Elevated progesterone stimulates an increase in the intracellular secondary messenger, cyclic adenosine monophosphate (cAMP), which sensitizes stromal cells to progesterone through activation of the protein kinase A (PKA) pathway, and subsequent activation of progesterone receptor targets involved in the decidualization process.[8,9,10] During this MET, mesenchymal cells are transformed, losing their front–rear polarity and acquiring epithelial apical–basal polarity characteristics. N-cadherin expression is replaced by E-cadherin, vimentin levels decrease and Snail expression is increased.[11,12]
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