Serum miRNAs as potential biomarkers for exposure to embedded military-relevant metals

Many veterans live with military grade heavy metal fragments retained in soft tissue. Retained heavy metal fragments may negatively impact health in various organ systems and can manifest as gastrointestinal, neurocognitive, pulmonary and renal disturbances. As such, a better understanding of the long-term effects of retained metals and identification of biomarkers indicative of detrimental health outcomes would benefit clinical decision making. In this study, we analyzed serum microRNAs from rats with military-relevant pure metals implanted in the gastrocnemius muscle for 1, 3, 6, and 12 months in order to identify potential microRNA biomarkers that are indicative of exposure to one or more metals. Three month old, male, Sprague-Dawley rats (n=8/group) were surgically implanted with one of eight metals of interest (W, Ni, Co, Fe, Cu, Al, Pb, and DU) or tantalum (Ta); Ta, serves as a surgical procedure control because it has been shown to be inert when embedded in skeletal muscle. Serum was collected from each rat at 1, 3, 6, and 12 months after surgically implanting two metal pellets (1 mm diameter x 2 mm length) into each gastrocnemius muscle. Small RNA sequencing was performed on RNA isolated from serum samples.