Transcriptome profiling and functional analysis of sheep fed with high zinc-supplemented diet: A nutrigenomic approach

Zinc (Zn) is crucial to animals’ growth and homeostasis, as it actively regulates transcription factors, DNA, and protein synthesis. To date, there is little information on the Zn-induced transcriptomic changes in small ruminants. Therefore, the present study investigated the nutrigenomics- related effects of dietary Zn in sheep. Fifteen lactating crossbred ewes (3–4 years of age and 55–65 kg body weight) were acclimated to indoor individual pen feeding of a basal control diet, that contained Zn, in the form of Zn oxide (ZnO, 79 mg/animal/day), for 2 weeks. Using a randomized pretest-posttest control group design, sheep were then assigned to two groups. For 40-days, the first group (n =5) kept receiving the basal diet and served as a control (CTR), while the other group (n= 10, group Zn) received high dietary Zn diet, in the form of Zn sulphate monohydrate (ZnSO4·H2O, 291 mg/animal/day). Whole blood was collected from each group at 2 time-points [beginning (T0), and after 40-days of the extra Zn supplementation (T40)], then total RNA was isolated. The microarray analysis of 30 samples (15 animal x 2 time-points), evidenced (fold-change ≥2, adjusted P-value< 0.05) 154 unique differentially expressed genes (DEGs) in the Zn group (T40 versus T0), while no genes were differentially expressed in the CTR group. Functional analysis of the DEGs showed the enrichment of cardiovascular-related, extracellular matrix, and immune-system-related pathways, several signal transduction and membrane permeability-related biological processes, as well as ion channels and zinc ion binding molecular functions. This study provides evidence on the dietary Zn-supplementation-induced transcriptomic signature in sheep, that mainly reflects transcriptional-modulation, induced immunity, and disrupted cardiac contraction patterns.