title: MicroRNA-regulated molecular mechanism underlying bovine subclinical endometritis.
abstract: An impaired uterine environment triggered by the incidence of subclinical endometritis often compromises fertility in the bovine. The uterus is a dynamic organ with tight regulation of specific genes at the transcriptional and translational levels. Herein, we hypothesised that subclinical endometritis alters the expression of uterine microRNAs (miRNAs), which may result in the dysregulation of corresponding target genes and biological pathways. To test this hypothesis, we used a genome-wide RT(2) (Exiqon, Vedbaek, Denmark) miRNA PCR array consisting of 354 miRNA primers and analysed miRNA expression in uterine cytobrush samples taken from cows with and without subclinical endometritis. The results revealed aberrant expression of 23 miRNAs in cows with subclinical endometritis compared with healthy cows. Furthermore, we designed an in vitro endometrial cell culture model challenged by lipopolysaccharide (LPS) to validate the differential regulation of miRNAs in cytobrush samples. Interestingly, we observed similar expression miRNA patterns in cytobrush samples taken from cows with or without subclinical endometritis and in vitro cultured endometrial cells challenged by LPS. To trace signalling pathways and biological functions potentially controlled by the aberrantly expressed miRNAs, we filtered high-ranking target genes from miRBase and analysed them using ingenuity pathway analysis. The gene networks, canonical pathways and biological functions strikingly converged to signalling pathways that mediate inflammatory responses, cellular proliferation, cell movement, the cell cycle and apoptosis in the bovine endometrium. In addition, expression analysis of key genes from the gene networks confirmed their presence and the potential regulation of these genes by uterine miRNAs. Furthermore, luciferase assay data substantiated the primary information from bioinformatic prediction that generated potential target genes for the dysregulated miRNAs in subclinical endometritis. Together, these data suggest the potential regulatory role of uterine miRNAs in the development and progression of bovine subclinical endometritis.
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hailemariam
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ibrahim
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hoelker
authors.affiliation: University of Veterinary Medicine Vienna, Herd Management in Ruminants, Veterinärplatz 1, A-1210 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Drillich
authors.affiliation: Clinic for Reproduction, Section of Production Medicine and Quality Management, Free University of Berlin, Königsweg 63, 14163 Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Heuwieser
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Looft
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: M U
authors.initials: MU
authors.lastname: Cinar
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Tholen
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schellander
authors.affiliation: Institute of Animal Science, Animal Breeding and Husbandry Group, University of Bonn, Endenicher Allee 15, 53115 Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Tesfaye
mesh_terms: D000818:Animals; D058345:Asymptomatic Infections; D002417:Cattle / Q000235:genetics*; D002418:Cattle Diseases / Q000235:genetics*; D002478:Cells, Cultured; D004716:Endometritis / Q000235:genetics* / Q000473:pathology / Q000662:veterinary; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides; D035683:MicroRNAs / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D014599:Uterus / Q000378:metabolism / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D035683:MicroRNAs