11 Transcriptomic changes in response to form of selenium on the interferon-tau signaling mechanism in the caruncular tissue of beef heifers at maternal recognition of pregnancy
Authors: Carr Sarah , Crites Benjamin , Bridges Phillip 
Published: March 2024

Abstract
It is necessary to supplement selenium (Se) to the diet of beef cattle in regions where the soils and forages are deficient in this trace mineral. Supplementation with Se conventionally occurs using an inorganic form (ISe) although the organic forms (OSe) are available when cattle consume forage. Previously we have investigated the effects of supplemental Se as ISe, or a 1:1 mixture of ISe to OSe (MIX) on grazing beef cows and heifers and have observed significant effects on the corpus luteum (CL) and endometrium. The MIX form of Se increased systemic progesterone (P4) during the early luteal phase of the estrous cycle at a time that can significantly improve early embryonic development. We subsequently investigated the effects of MIX form Se versus ISe on the mRNA transcripts encoding IFNτ- and P4-induced proteins in the caruncular (CAR) tissue of the uterine endometrium at maternal recognition of pregnancy (MRP). MIX-supplemented heifers had a decrease in the relative abundance of mRNAs encoding DGAT2, FGF2, IFIT3, ISG15, MX1, OAS2, and RSAD2 in CAR which was coupled with significantly longer conceptuses at MRP. Presently, we examined transcriptomic changes in the CAR tissue of the endometrium at MRP. Angus-cross heifers (n = 20) were exposed to a 45-d period of Se depletion (no supplemental Se) followed by a 45-day repletion period with ISe alone. Heifers were then randomly assigned to 90 days of treatment with a vitamin-mineral mix containing 35-ppm Se as ISe (n = 10), or 1:1 mixture of ISe and OSe (n = 10, MIX). Following insemination, heifers were killed at MRP (d 17) and their reproductive tracts collected. Only heifers with a fully intact recovered conceptus were utilized for further analyses (n = 6 per treatment). Transcriptomic analysis using RNA-sequencing was conducted using total mRNA from CAR biopsies. Differential gene expression was determined using Integrated Differential Expression and Pathway Analysis (iDEP.96), and DEG were subjected to canonical, functional, and network analyses using QIAGEN’s Ingenuity Pathway Analysis (IPA). RNA sequencing results were validated using qPCR. At P &lt; 0.05, there was a total of 2,029 DEGs with 1,038 transcripts upregulated, and 991 transcripts downregulated in MIX versus ISe heifers. Saliently, the interferon JAK/STAT pathway signaling through the STAT1/2 heterodimer was significantly down regulated in CAR samples from MIX heifers, as were the following interferon-responsive genes: IFIT1, IFIT2, IFIT3, IRF1, IRF9, ISG15, ISG20, OAS2, RSAD2, and STAT2. Additionally, there were significant changes in mRNA contribution to the immunotolerant environment (IDO1, ISG20, SCARA1, and TGFB1) to allow the fetal allograft to closely interact with the maternal interface. In combination, these findings suggest more advanced preparation of the CAR and developing conceptus for placentation and to evade immune rejection by the maternal endometrium during implantation.