Peroxisome proliferator activated receptor gamma (PPAR-γ) ligand pioglitazone regulated gene networks in term human primary trophoblast cells

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 81; pp. 99 - 107
• Main Authors: El Dairi, Rami, Huuskonen, Pasi, Pasanen, Markku, Rysä, Jaana
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2018
• Subjects: Cells, Cultured; Female; Gene expression profiling; Gene Expression Regulation - drug effects; Gene Regulatory Networks; Humans; Hypoglycemic Agents - pharmacology; Ligands; Pathway analysis; Peroxisome proliferator-activated receptor -γ; Pioglitazone; Pioglitazone - pharmacology; Placenta - cytology; PPAR gamma; Pregnancy; Transcriptome - drug effects; Trophoblast; Trophoblasts - drug effects; Trophoblasts - metabolism; CXCL; EVCT; SCT; Gene expression profiling; LRP5; Trophoblast; VLDLR; hCG; TNF; Pathway analysis; MUC1; PPAR; HMOX1; CYP; IL; ELOVL4; VEGF; Pioglitazone; STAT3; CCL; GEO; CT; MMP; Peroxisome proliferator-activated receptor -γ; PAH; BNF; IPA; S100A8
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2018.07.077

•The effect of PPAR-γ agonist pioglitazone on human placental gene expression was evaluated.•Pioglitazone differentially regulated gene expression of 79 genes in term primary trophoblasts.•Dysregulated genes were involved in cellular growth, inflammatory and immunomodulatory response and lipid metabolism.•PPAR-γ could be important for placental immunological protection. Peroxisome proliferator-activated receptor (PPAR-γ) is a nuclear receptor that is highly expressed in placenta. In this study, the PPAR-γ regulated gene networks were characterized in human primary trophoblast cells in vitro. The trophoblasts were isolated from full term placenta after delivery and exposed to 20 μM of the PPAR-γ agonist, pioglitazone, for 72 h and gene expression profiles were examined. Differential expression of selected genes was confirmed with RT-qPCR. Ingenuity pathway analysis was performed to identify PPAR-γ induced biological functions and downstream signaling pathways. In response to pioglitazone treatment, 37 genes were upregulated and 42 genes were downregulated as compared to control cells. The upregulated genes included those involved in metabolic pathways, whereas the expressions of many cytokines and chemokines were downregulated. Our data indicate that PPAR-γ possesses pleiotropic functions also in term trophoblasts regulating genes especially involved in cellular growth and proliferation, inflammatory and immunomodulatory responses and lipid metabolism.