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

Reprod Toxicol. 2018 Oct:81:99-107. doi: 10.1016/j.reprotox.2018.07.077. Epub 2018 Jul 19.

Abstract

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.

Keywords: Gene expression profiling; Pathway analysis; Peroxisome proliferator-activated receptor -γ; Pioglitazone; Trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Female
  • Gene Expression Regulation / drug effects*
  • Gene Regulatory Networks
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Ligands
  • PPAR gamma
  • Pioglitazone / pharmacology*
  • Placenta / cytology*
  • Pregnancy
  • Transcriptome / drug effects
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism

Substances

  • Hypoglycemic Agents
  • Ligands
  • PPAR gamma
  • Pioglitazone