Uptake and function studies of maternal milk-derived miRNAs. Mus musculus

MicroRNAs are important regulators of cell-autonomous gene expression that influences many biological processes. They are also released from cells and are present in virtually all body fluids, including blood, urine, saliva, sweat, and milk. The functional role of extracellular miRNAs is controversial, and irrefutable demonstration of miRNA uptake by cells and canonical miRNA function is still lacking. Here we show that miRNAs are present at high levels in milk of lactating mice. To investigate intestinal uptake of miRNAs in newborn mice, we employed genetic models in which newborn miR-375 and miR-200c KO mice received milk from wildtype foster mothers. Analysis of intestinal epithelium, blood, liver and spleen revealed no evidence for miRNA uptake. miR-375 levels in hepatocytes were at the limit of detection and remained orders of magnitude below the threshold for target gene regulation (between 1000 and 10,000 copies/cell). Furthermore, our study revealed rapid degradation of milk miRNAs in the intestinal fluid. Together, our results indicate a nutritional rather than gene regulatory role of miRNAs in milk of newborn mice. Overall design: miRNA profiling of WT murine milk clots from day 2, day 8, and day 14 of lactation, with 2 biological replicates per day.