Mouse placental microRNA profiling upon zearalenone (ZEA) exposure.

Mycoestrogen zearalenone (ZEA) is a common food contaminant (ppb ~ low ppm levels) that can interfere with female reproduction. Previously we demonstrated disrupted mouse placental development by 40 ppm ZEA diet. MicroRNAs are sensitive to xenobiotics and have been implicated in placental physiology and pathology. We hypothesized that ZEA could dysregulate microRNA expression in the mouse placenta. Young mice were fed with 0 ppm (control), 4 ppm, and 40 ppm ZEA diets from 5.5 days post-coitum (D5.5). On D13.5, placentas were isolated for microRNA array analysis. In the D13.5 control placentas, ~ 80% of microRNAs had an average signal intensity < 100; the top 20 most abundant microRNAs were predicated to target genes involved in metabolism, vesicle trafficking, and immune function, etc., that are critical for maternal-fetal communications. Using criteria of Log2FC ≥ 1 and Log2FC ≤ -1 (linear 2 fold change (FC)), a false discovery rate adjusted p-value ≤ 0.05, and an average signal intensity in all three groups > 100, R package limma identified 8 differentially expressed miRNAs (mmu-miR-133b-5p, mmu-miR-7028-5p, mmu-miR-294-3p, mmu-miR-3970, mmu-miR-20b-5p, mmu-miR-7683-3p, mmu-miR-335-5p, mmu-miR-450b-5p) in the 40 ppm ZEA group that included all 5 differentially expressed miRNAs in the 4 ppm ZEA group. The predicted targets of the 5 differentially expressed microRNAs in both ZEA-treated groups were related to immune function, protein metabolism and post-translational modifications, extracellular matrix organization, and membrane trafficking, etc. These data imply roles of placental microRNAs in regulating expression of genes critical for placental function in vivo and in sensing environmental contaminants.