title: Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility.
abstract: BACKGROUND
  Contamination of the uterine lumen with bacteria is ubiquitous in cattle after parturition. Some animals develop endometritis and have reduced fertility but others have no uterine disease and readily conceive. The present study tested the hypothesis that postpartum cattle that develop persistent endometritis and infertility are unable to limit the inflammatory response to uterine bacterial infection.
  
  
  METHODS
  Endometrial biopsies were collected several times during the postpartum period from animals that were subsequently infertile with persistent endometritis (n = 4) or had no clinical disease and conceived to first insemination (n = 4). Quantitative PCR was used to determine the expression of candidate genes in the endometrial biopsies, including the Toll-like receptor (TLR 1 to 10) family of innate immune receptors, inflammatory mediators and their cognate receptors. Selected proteins were examined by immunohistochemistry.
  
  
  RESULTS
  The expression of genes encoding pro-inflammatory mediators such as interleukins (IL1A, IL1B and IL6), and nitric oxide synthase 2 (NOS2) were higher during the first week post partum than subsequently. During the first week post partum, there was higher gene expression in infertile than fertile animals of TLR4, the receptor for bacterial lipopolysaccharide, and the pro-inflammatory cytokines IL1A and IL1B, and their receptor IL1R2. The expression of genes encoding other Toll-like receptors, transforming growth factor beta receptor 1 (TGFBR1) or prostaglandin E2 receptors (PTGER2 and PTGER4) did not differ significantly between the animal groups. Gene expression did not differ significantly between infertile and fertile animals after the first week postpartum. However, there were higher ratios of IL1A or IL1B mRNA to the anti-inflammatory cytokine IL10, during the first week post partum in the infertile than fertile animals, and the protein products of these genes were mainly localised to the epithelium of the endometrium.
  
  
  CONCLUSIONS
  Cattle may maintain fertility by limiting the inflammatory response to postpartum bacterial infection in the endometrium during the first week after parturition.
authors.affiliation: Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, UK. shanherath74@hotmail.com
authors.forename: Shan
authors.initials: S
authors.lastname: Herath
authors.forename: Sonia T
authors.initials: ST
authors.lastname: Lilly
authors.forename: Natalia R
authors.initials: NR
authors.lastname: Santos
authors.forename: Robert O
authors.initials: RO
authors.lastname: Gilbert
authors.forename: Leopold
authors.initials: L
authors.lastname: Goetze
authors.forename: Clare E
authors.initials: CE
authors.lastname: Bryant
authors.forename: John O
authors.initials: JO
authors.lastname: White
authors.forename: James
authors.initials: J
authors.lastname: Cronin
authors.forename: I Martin
authors.initials: IM
authors.lastname: Sheldon
mesh_terms: D000818:Animals; D001706:Biopsy; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D004717:Endometrium / Q000276:immunology* / Q000473:pathology; D005260:Female; D005298:Fertility / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D007239:Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary; D007247:Infertility, Female / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D051218:Lymphocyte Antigen 96 / Q000235:genetics; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics; D049590:Postpartum Period / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D011982:Receptors, Prostaglandin / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics; D014591:Uterine Diseases / Q000235:genetics / Q000276:immunology / Q000662:veterinary
chemical_list: D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D053474:Nod1 Signaling Adaptor Protein; D011982:Receptors, Prostaglandin; D018125:Receptors, Transforming Growth Factor beta; D051193:Toll-Like Receptors; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D017493:Leukocyte Common Antigens