Mouse placental microRNA profiling upon zearalenone exposure

Mycoestrogens are derived from mold and can interfere with female reproduction. Mycoestrogen zearalenone (ZEA) is a common food contaminant in levels of ppb ~ low ppm. 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. Gestation day 13.5 (D13.5) placentas from young mice treated with 0 ppm (control), 4 ppm, and 40 ppm ZEA diets were analyzed for microRNA profiling using microRNA array. The top 20 most highly expressed microRNAs in the D13.5 control placentas are predicated to target genes involved in important signaling pathways that are critical for maternal-fetal communications, such as protein processing in endoplasmic reticulum, endocytosis, and regulation of actin cytoskeleton. Using criteria of Log2FC ≥ 1 and Log2FC ≤ -1 (linear 2 fold change (FC)), a false discovery rate adjusted p-value ≤ 0.05, and average reading > 100 (top 20% most abundant microRNAs), 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-291b-3p, mmu-miR-369-3p) in the 40 ppm ZEA group that included all 4 differentially expressed miRNAs in the 4 ppm ZEA group. Some of these differentially expressed microRNAs have been shown in vitro to have important functions in placental growth and maternal-fetal transport. These data imply roles of placental microRNAs in regulating expression of genes critical for placental function in vivo and in sensing environmental contaminants. D13.5 placentas from mice fed 0 ppm (control), 4 ppm, or 40 ppm zearalenone (n=4/group) were used for the array.