title: Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows.
abstract: BACKGROUND
  All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP) which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR).
  
  
  RESULTS
  mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P < 0.1) included the T cell receptor signalling pathway, graft-versus-host disease and cytokine-cytokine receptor interaction pathways. However 30 DPP, where the majority of genes were differentially expressed, the enrichment (adjusted P < 0.1) of tissue repair and proliferative activity pathways was observed. Nineteen candidate genes selected from mRNA-Seq results, were independently assessed by qRT-PCR in additional postpartum cows (5 animals) at both time points. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum.
  
  
  CONCLUSIONS
  The results of this study reveal an early activation of the immune response which undergoes a temporal functional change toward tissue proliferation and regeneration during endometrial involution in healthy postpartum cows. These molecular changes mirror the activation and resolution of endometrial inflammation during involution previously classified by the degree of neutrophil infiltration. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes may become potential markers for resolution of endometrial inflammation in the postpartum cow.
authors.affiliation: Animal and Bioscience Research Department, Animal & Grassland Research and Innovation Centre, Teagasc, Grange, Co, Meath, Ireland.
authors.forename: Cathriona
authors.initials: C
authors.lastname: Foley
authors.forename: Aspinas
authors.initials: A
authors.lastname: Chapwanya
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Creevey
authors.forename: Fernando
authors.initials: F
authors.lastname: Narciandi
authors.forename: Derek
authors.initials: D
authors.lastname: Morris
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Kenny
authors.forename: Paul
authors.initials: P
authors.lastname: Cormican
authors.forename: John J
authors.initials: JJ
authors.lastname: Callanan
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
authors.forename: Kieran G
authors.initials: KG
authors.lastname: Meade
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004716:Endometritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000662:veterinary*; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D008969:Molecular Sequence Data; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology
chemical_list: D017931:DNA Primers