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Human villous cytotrophoblast: Rosiglitazone treated (RT-VCT) vs. Control (VCT)

ABSTRACT: Trophoblasts, as the main part of placenta, undergo cell differentiation including invasion, migration, and fusion. Abnormalities in these processes can lead to a series of gestational diseases whose underlying mechanisms are still unclear. The peroxisome proliferator-activated receptor γ (PPARγ), expressed in the nuclei of extravillous trophoblasts (EVCTs) at the first trimester and villous cytotrophoblasts (VCTs) throughout the pregnancy, is proved to be essential in placentation. We aimed to explore the genome-wide effects of PPARγ on EVCTs and VCTs by the treatment of PPARγ agonist rosiglitazone. EVCTs and CTs were purified from human chorionic villi, followed by primary culture and rosiglitazone treatment. Transcriptomes of EVCTs and VCTs were performed by microarray experiments (Affymetrix and Axon). Owing to the different platforms, threshold for differentially expressed genes (DEGs) detection was performed based on 1.5-fold change and 5% FDR for EVCTs gene expression while 1% FDR was set for VCTs gene expression. Gene ontology (GO) annotation and pathways analysis of DEGs were conducted with ClueGO. PPARγ and DEGs protein interactions predicted by online tool STRING, while PPARγ and DEGs promoters binding sites prediction was conducted by iRegulon. GO and pathway terms were compared between EVCTs and VCTs through ClusterProfiler. Visualization was achieved and modified by Cytoscape. Our microarray data showed that 139 DEGs were detected in rosiglitazone-treated EVCTs (RT-EVCTs) and 197 DEGs in rosiglitazone-treated VCTs (RT-VCTs). Downstream annotation analysis showed the commons and differences between RT-EVCTs and RT-VCTs, including biological process, molecular function, cellular component, KEGG pathway and protein-protein-interaction and transcription factor – target gene binding site prediction. To sum up, our results provide a sight of view to PPARγ-activated trophoblasts performances by giving transcriptomic signatures of the RT-EVCTs and RT-VCTs and make it feasible to acquire more information for further research and find out possible drug-targeted genes or pathways in human placenta.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137434 | GEO | 2020/04/24

REPOSITORIES: GEO

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Project description:Genomic expression profiles of blood and placenta reveal significant immune-related pathways and categories in Chinese women with Gestational Diabetes Gestational diabetes mellitus (GDM) is a complex metabolic disease which occurs in pregnancy with high prevalence, and its pathogenesis remains elusive. Thus far, there has been no comprehensive gene expression profiling in Chinese women with GDM. In this study, we attempt to define the genes and/or pathways that are involved in GDM with Chinese ethnicity, by the Illumina microarray technique. We found 5,197 and 243 genes with significantly altered expression due to GDM in blood and placenta tissues, respectively. Previously known genes (such as TNF, IL1B, LEP, IFNG, and HLA-G) with altered gene expression in GDM were also validated here. In addition, we identified undescribed genes VAV3, PTPN6, CD48 and IL15, in which expression was related to GDM by microarray and Q-RT-PCR assays. To identify GDM-associated pathways, we used analyses with integrated functional annotation (i.e. KEGG) and extracted two significant pathways, which were Natural killer cell mediated cytotoxicity (hsa04650; FDR = 7.10E-09) in blood and Cytokine-cytokine receptor interaction (hsa04060; FDR = 1.07E-03) in placenta tissues. Immune system process (GO: 0002376) was identified by GO analysis with FDR P-value = 7.01E-60 in blood and FDR P-value = 3.57E-08 in placenta tissues, indicating the importance of immunological and inflammatory categories in GDM. Furthermore, despite differences in the quantity of gene expression, we observed a similar functional distribution between expression of blood and placenta tissues in GDM under the categories of immunity. These newly identified key genes and pathways may provide valuable information for the pathogenesis of GDM and advance disease diagnosis, prevention, medication design, and clinical treatment of the disease. One individual GDM blood tissue sample and one pooled GDM blood tissue sample were compared to one pooled healthy blood tissue sample. One pooled GDM placenta tissue sample was compared to one pooled healthy placenta tissue sample.

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Human villous cytotrophoblast: Rosiglitazone treated (RT-VCT) vs. Control (VCT)

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