Form of dietary selenium affects mRNA encoding cholesterol biosynthesis and immune response elements in the early luteal phase bovine corpus luteum

Widespread regions of the southeast United States have soils, and hence forages, deficient in selenium (Se), necessitating Se supplementation to grazing cattle for optimal immune function, growth, and fertility. We have reported that supplementation with an isomolar 1:1 mix (MIX) of inorganic (ISe) and organic (OSe) forms of Se increases early luteal phase (LP) progesterone (P4) above that in cows on ISe alone. Increased early LP P4 advances embryonic development. Our objective was to determine the effect of form of Se on the transcriptome of the early LP corpus luteum (CL) with the goal of elucidating form of Se-regulated processes affecting luteal steroidogenesis and function. Non-lactating, 3-yr-old Angus-cross cows underwent 45-d Se-depletion, then repletion periods, and then at least 90 d of supplementation (TRT) with 35 ppm Se/d as either ISe (n = 5) or MIX (n = 5). CL were then recovered on day 7 of the estrous cycle, total RNA isolated, and the effect of TRT on the luteal transcriptome evaluated using bovine gene 1.0 ST arrays (Affymetrix, Inc., Santa Clara, CA). The abundance of transcripts in each CL was subjected to one-way ANOVA using Partek Genomic Suite software to determine TRT effects. Microarray analysis indicated a total of 887 transcripts that were differentially expressed and functionally annotated, with 423 and 464 up- and down-regulated (P < 0.05) in MIX vs. ISe CL, respectively. Bioinformatic analysis (Ingenuity Pathway Analysis) revealed the top TRT-affected canonical pathways to include seven specific to cholesterol biosynthesis and two to inflammatory responses. Results from the microarray analysis were corroborated by targeted real-time PCR. MIX CL had increased (P < 0.05) abundance of transcripts regulating cholesterol biosynthesis including DHCR7, DHCR24, and CYP51A1 (fold changes of 1.65, 1.48, and 1.40, respectively), suggesting MIX-induced increases in P4 to be due, in part, to increased availability of substrate to luteal cells. In addition, MIX CL had increased (P < 0.05) abundance of immune-response transcripts including C1QC, FAS, ILR8B, and IL1R1 (fold changes of 2.30, 1.74, 1.66, and 1.63, respectively). SREBF1 mRNA was also increased (1.32-fold, P < 0.05) in the MIX CL, which increases cholesterol synthesis and stimulates IL1B, linking effects of form of supplemental Se (TRT) on cholesterol biosynthesis and immune function in the CL. The form of supplemental Se provided to cattle affects early luteal phase concentrations of progesterone, which is known to affect development of the conceptus, via changes in cholesterol biosynthesis and immune function in the corpus luteum. Lay Summary In regions with soils deficient in selenium (Se), producers should supplement this trace mineral to the diet of forage-grazing cattle. We previously reported that circulating concentrations of progesterone (P4) are affected by the form of Se supplemented to cows. In this report, we aimed to determine how the form of Se affects the transcriptome of the bovine CL, with the goal of elucidating form of Se effects on luteal steroidogenesis. Cows were supplemented with the industry standard, an inorganic form of Se, or a 1:1 mix of organic and inorganic forms (MIX), with corpora lutea recovered on day 7 of the estrous cycle. The effect of TRT (form of Se) on the luteal transcriptome was then evaluated using bovine gene 1.0 ST arrays (Affymetrix, Inc., Santa Clara, CA), with the results of the microarray analysis corroborated by targeted qPCR. Treatment altered >800 transcripts in the CL, including those regulating cholesterol biosynthesis and immune function. The effect of form of Se on luteal steroidogenesis appears to be the result of changes in cholesterol biosynthesis and uptake by luteal cells, with cross talk between immune and cholesterol regulatory pathways also apparent.

Automated summary

Supplementing grazing cattle in selenium-deficient regions with an isomolar 1:1 mix of inorganic and organic selenium can increase early luteal phase progesterone levels, promoting embryonic development. The form of supplemental selenium affects the luteal transcriptome, regulating cholesterol biosynthesis and immune function in the corpus luteum.