Aflatoxin B1 targeted gene expression profiles in human placental primary trophoblast cells

Abstract

Aflatoxin B1 (AFB1) is a mycotoxin produced by Aspergillus flavus and A. parasiticus. A high exposure (40 nM and 1 µM AFB1 for 72 h) was used to study mechanistic effects of AFB1 on gene expression patterns in human primary trophoblast cells, isolated from full term placentae after delivery. Gene expression profiling was conducted, and Ingenuity pathway analysis (IPA) software was used to identify AFB1-regulated gene networks and regulatory pathways.

In response to 40 nM AFB1, only 7 genes were differentially expressed whereas 1 µM AFB1 significantly dysregulated 170 genes (124 down- and 46 upregulated, ±1.5-fold, p < 0.05) in AFB1-exposed trophoblasts when compared to controls. The top downregulated genes were involved in endocrine signalling and biosynthesis of hormones, and lipid and carbohydrate metabolism. The top upregulated genes were involved in protein synthesis and regulation of cell cycle. The main canonical pathways identified by IPA were associated with endocrine signalling including growth hormone signalling, and corticotropin releasing hormone signalling. Furthermore, genes involved in aryl hydrocarbon receptor (AhR)-mediated estrogen receptor signalling were dysregulated in response to AFB1.

Our findings indicate that a high concentration 72 h AFB1 exposure caused relatively moderate number of changes on transcript level to human placental primary trophoblast cells. However, these preliminary results need to be confirmed with human-relevant concentrations of AFB1.