Effects of conceptus proteins on endometrium and blood leukocytes of dairy cattle using transcriptome and meta-analysis

This study investigates the short and long-term effects of IFNT and PAG on the transcriptome of endometrium and blood leukocytes. Holstein heifers received intrauterine infusions of one of the following treatments: 20 mL of a 200 g/mL bovine serum albumin solution (BSA; vehicle) from day 14 to 16 of the estrous cycle (BSA), vehicle + 10 g/mL of IFNT from day 14 to 16 (IFNT3), vehicle + 10 g/mL of IFNT from day 14 to 19 (IFNT6), and vehicle + 10 g/mL of IFNT from day 14 to 16 followed by vehicle + 10 g/mL of IFNT + 5 g/mL of PAG from day 17 to 19 (IFNT+PAG). RNA-seq analysis was performed in endometrial biopsies and blood leukocytes collected after treatments. Acute IFNT signaling in the endometrium (IFNT3 vs BSA), induced differentially expressed genes (DEG) associated with interferon activation, immune response, inflammation, cell death, and inhibited vesicle transport and extracellular matrix remodeling. Prolonged IFNT signaling (IFNT6 vs IFNT3) altered gene expression related to cell invasion, retinoic acid signaling, and embryo implantation. In contrast, PAG induced numerous DEG in blood leukocytes but only 4 DEG in the endometrium. In blood leukocytes, PAG stimulated genes involved in development and TGFB signaling while inhibiting interferon signaling and cell migration. Overall, IFNT is a primary regulator of endometrial gene expression, while PAG predominantly affected the transcriptome of circulating immune cells during early pregnancy. Further research is essential to fully grasp the roles of identified DEG in both the endometrium and blood leukocytes. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=70 SRC="FIGDIR/small/591148v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@b51110org.highwire.dtl.DTLVardef@173433dorg.highwire.dtl.DTLVardef@4368e5org.highwire.dtl.DTLVardef@19bd118_HPS_FORMAT_FIGEXP M_FIG C_FIG Main findingsO_LIAcute IFNT signaling in the endometrium activates genes involved in inflammation while inhibiting vesicle transport in cells and ECM remodeling. C_LIO_LIProlonged IFNT signaling in the endometrium regulates genes involved in cell invasion and retinoic acid signaling. C_LIO_LIPAG alter gene expression in blood leukocytes more than in endometrium and may stimulate leukocyte differentiation while inhibiting leukocyte extravasation. C_LI