Transcriptome analysis of umbilical cord mesenchymal stem cells revealed fetal programming due to chorioamnionitis

Although chorioamnionitis (CAM) has been demonstrated to be associated with numerous short- and long-term morbidities, the precise mechanisms remain unclear. One of the reasons for this is the lack of appropriate models for analyzing the relationship between the fetal environment and chorioamnionitis and fetal programming in humans. In this study, we aimed to clarify the fetal programming caused by CAM using the gene expression profiles of UCMSCs. From nine preterm neonates with CAM (n = 4) or without CAM (n = 5), we established UCMSCs. The gene expression profiles obtained by RNA-seq analysis revealed distinctive changes in the CAM group USMSCs. The UCMSCs in the CAM group had a myofibroblast-like phenotype with significantly increased expression levels of myofibroblast-related genes, including alpha-smooth muscle actin (p < 0.05). In the pathway analysis, the genes involved in DNA replication and G1 to S cell cycle control were remarkably decreased, suggesting that cellular proliferation was impaired, as confirmed by the cellular proliferation assay (p < 0.01-0.05). Pathway analysis revealed that genes related to white fat cell differentiation were significantly increased. Our results could explain the long-term outcomes of patients who were exposed to CAM and revealed that UCMSCs could be an in vitro model of fetal programming affected by CAM.

Automated summary

This study aimed to clarify the fetal programming caused by chorioamnionitis (CAM) using gene expression profiles of umbilical cord mesenchymal stem cells (UCMSCs). The results revealed distinctive changes in UCMSCs from the CAM group, including increased expression levels of myofibroblast-related genes and impaired cellular proliferation. Pathway analysis also showed increased expression of genes related to white fat cell differentiation. These findings provide insights into the long-term outcomes of patients exposed to CAM and highlight the potential of UCMSCs as an in vitro model for studying CAM-induced fetal programming.