Aryl hydrocarbon receptor (AhR) agonist β-naphthoflavone regulated gene networks in human primary trophoblasts

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in placenta. AhR belongs to a class of transcriptional regulators that control many developmental and physiological events (e.g. xenobiotic metabolism). Our study describes AhR regulated transcriptional responses in human primary trophoblast by using the AhR agonist, β-naphthoflavone (BNF). Human primary trophoblast cells were isolated from full term placenta after delivery. The trophoblasts were exposed to 25 μM of AhR agonist, BNF, for 72 hours. Gene expression profiling was conducted with Illumina HT-12 expression beadchips. Expression of selected genes was confirmed with RT-qPCR. Ingenuity pathway analysis (IPA) was used to predict functional pathways and upstream regulators of differentially expressed genes in order to identify regulatory networks associated with AhR. In response to BNF exposure, 64 genes were upregulated, and 257 genes were downregulated compared to control trophoblasts (±1.5-fold, p < 0.05). BNF regulated genes included placental hormones and genes implicated in immune- and inflammatory responses in addition to their well-known effects on xenobiotic metabolism, oxidative stress, antioxidant defense. In conclusion, these results show that BNF has wide-ranging effects on placental gene expression beyond xenobiotic metabolism e.g. disruption of inflammatory processes and hormones in the placenta.