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Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells.

ABSTRACT: The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ECM stiffness on various aspects of human trophoblast cell behaviors during cell-ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness. The human choriocarcinoma (JAR) cell lineage was used as the trophoblast model. We found that the spreading area of JAR cells, the formation of focal adhesions, and the polymerization of the F-actin cytoskeleton were all facilitated with increased ECM stiffness. Significantly, JAR cells also exhibited durotactic behavior on ECM with a gradient stiffness. Meanwhile, stiffness of the ECM affects the invasion of multicellular JAR spheroids. These results demonstrated that human trophoblast cells are mechanically sensitive, while the mechanical properties of the uterine microenvironment could play an important role in the implantation process.

SUBMITTER: Cao J

PROVIDER: S-EPMC10045595 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells.

Cao Jialing J Li Hangyu H Tang Hongyan H Gu Xuenan X Wang Yan Y Guan Dongshi D Du Jing J Fan Yubo Y

Bioengineering (Basel, Switzerland) 20230321 3

The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ECM stiffness on various aspects of human trophoblast cell behaviors during cell-ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness. The human choriocarcinoma (JAR) cell lineage was used as the ...[more]

PMID: 36978775

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Project description:Trophoblast stem (TS) cells were first isolated from the mouse placenta; however, little is known about their maintenance and niche in vivo. TS cells, like other stem cells, have a unique microenvironment in which the extracellular matrix (ECM) is a component. Placental pathology is associated with ECM change. However, how these changes and the individual ECM components impact the maintenance or differentiation of TS cells has not been established. This study identified which ECM component(s) maintain the greatest expression of markers associated with undifferentiated mouse trophoblast stem (mTS) cells and which alter the profile of markers of differentiation based on mRNA analysis. mTS cells cultured on individual ECM components and subsequent quantitative polymerase chain reaction analysis revealed that laminin promoted the expression of markers associated with undifferentiated TS cells, fibronectin promoted gene expression associated with syncytiotrophoblast (SynT) layer II cells, and collagen IV promoted the expression of genes associated with differentiated trophoblast. To investigate whether pathological placental ECM influenced the expression of genes associated with different trophoblast subtypes, the mouse model of streptozotocin (STZ)-induced pancreatic β cell ablation and diabetes was used. Female mice administered STZ (blood glucose ≥300 mg/dL) or control (blood glucose ≤150 mg/dL) were mated. Placental pathology at embryonic day (E)14.5 was confirmed with reduced fetal blood space area, reduced expression of the pericyte marker αSMA, and decreased expression of ECM proteins. mTS cells cultured on ECM isolated from STZ placenta were associated with reduced expression of undifferentiated mTS markers and increased expression of genes associated with terminally differentiated trophoblast [Gcm-1 and SynA (SynT) and junctional zone Tpbpa and Prl2c2]. Altogether, these results support the value of using ECM isolated from the placenta as a tool for understanding trophoblast contribution to placental pathology.

Project description:BACKGROUND:In the bovine placenta, intimate fetomaternal contacts are restricted to discrete placentomes. Here, widely branched fetal chorionic villi interdigitate with corresponding maternal caruncular crypts. The fetal trophoblast epithelium covering the chorionic villi consists of approximately 80% uninucleate trophoblast cells (UTCs) and 20% binuclear trophoblast giant cells (TGCs). The weakly invasive TGCs migrate toward the caruncle epithelium and eventually fuse with individual epithelial cells to form short-lived fetomaternal hybrid cells. In this way, molecules of fetal origin are transported across the placental barrier and released into the maternal compartment. The UTC/TGC ratio in the trophoblast remains almost constant because approximately as many new TGCs are produced from UTCs as are consumed by the fusions. The process of developing TGCs from UTCs was insufficiently understood. Therefore, we aimed to detect differentially expressed genes (DEGs) between UTCs and TGCs and identify molecular functions and biological processes regulated by DEGs. RESULTS:We analyzed gene expression patterns in virtually pure UTC and TGC isolates using gene arrays and detected 3193 DEGs (p < 0.05; fold change values < - 1.5 or > 1.5). Of these DEGs, 1711 (53.6%) were upregulated in TGCs and 1482 (46.4%) downregulated. Gene Ontology (GO) analyses revealed that molecular functions and biological processes regulated by DEGs are related to the extracellular matrix (ECM) and its interactions with cellular receptors, cell migration and signal transduction. Furthermore, there was some evidence that O-glycan biosynthesis in TGCs may produce sialylated short-chain O-glycans (Tn antigen, core 1 O-glycans), while the synthesis of other O-glycan core structures required for the formation of complex (i.e., branched and long-chain) O-glycans appears to be decreased in TGCs. CONCLUSION:The differentiation of UTCs into TGCs particularly regulates genes that enable trophoblast cells to interact with their environment. Significant differences between UTCs and TGCs in ECM composition indicate reduced anchoring of TGCs in the surrounding matrix, which might contribute to their migration and their weakly invasive interaction with the maternal endometrium. Furthermore, increased expression of sialylated short chain O-glycans by TGCs could facilitate the modulation of maternal immune tolerance.

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Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells.

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Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells.

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