title: BVDV alters uterine prostaglandin production during pregnancy recognition in cows.
abstract: Embryonic mortality in cows is at least in part caused by failure of pregnancy recognition (PR). Evidence has shown that bovine viral diarrhoea virus (BVDV) infection can disrupt pregnancy. Prostaglandins (PG) play important roles in many reproductive processes, such as implantation. The aim of this study was to investigate the effect of BVDV infection on uterine PG production and PR using an in vitro PR model. Bovine uterine endometrial cells isolated from ten BVDV-free cows were cultured and treated with 0 or 100ng/mL interferon-τ (IFNT) in the absence or presence of non-cytopathic BVDV (ncpBVDV). PGF2α and PGE2 concentrations in the spent medium were measured using radioimmunoassays, and in the treated cells expression of the genes associated with PG production and signalling was quantified using qPCR. The results showed that the IFNT challenge significantly stimulated PTGS1 and PTGER3 mRNA expression and PGE2 production; however, these stimulatory effects were neutralised in the presence of ncpBVDV infection. ncpBVDV infection significantly increased PTGS1 and mPGES1 mRNA expression and decreased AKR1B1 expression, leading to increased PGE2 and decreased PGF2α concentrations and an increased PGE2:PGF2α ratio. The other tested genes, including PGR, ESR1, OXTR, PTGS2, PTGER2 and PTGFR, were not significantly altered by IFNT, ncpBVDV or their combination. Our study suggests that BVDV infection may impair PR by (1) inhibiting the effect of IFNT on uterine PG production and (2) inducing an endocrine switch of PG production from PGF2α to PGE2 to decrease uterine immunity, thereby predisposing the animals to uterine disease.
authors.affiliation: Department of Production and Population HealthRoyal Veterinary College, North Mymms, Hertfordshire, UK zcheng@rvc.ac.uk.
authors.forename: Zhangrui
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Life Science and Engineering CollegeNorthwest University for Nationalities, Lanzhou, China.
authors.forename: Ayimuguli
authors.initials: A
authors.lastname: Abudureyimu
authors.affiliation: Department of Production and Population HealthRoyal Veterinary College, North Mymms, Hertfordshire, UK.
authors.forename: Chike F
authors.initials: CF
authors.lastname: Oguejiofor
authors.affiliation: Department of Production and Population HealthRoyal Veterinary College, North Mymms, Hertfordshire, UK.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Ellis
authors.affiliation: Department of Production and Population HealthRoyal Veterinary College, North Mymms, Hertfordshire, UK.
authors.forename: Amy Teresa
authors.initials: AT
authors.lastname: Barry
authors.affiliation: Department of Production and Population HealthRoyal Veterinary College, North Mymms, Hertfordshire, UK Key Laboratory of Agricultural Animal GeneticsBreeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China zcheng@rvc.ac.uk.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology and Pathogen BiologyRoyal Veterinary College, North Mymms, Hertfordshire, UK.
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Anstaett
authors.affiliation: Department of Pathology and Pathogen BiologyRoyal Veterinary College, North Mymms, Hertfordshire, UK.
authors.forename: Joe
authors.initials: J
authors.lastname: Brownlie
authors.affiliation: Department of Production and Population HealthRoyal Veterinary College, North Mymms, Hertfordshire, UK.
authors.forename: D Claire
authors.initials: DC
authors.lastname: Wathes
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000188:drug therapy / Q000821:virology*; D002417:Cattle; D030241:Diarrhea Virus 1, Bovine Viral / Q000472:pathogenicity*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D005260:Female; D007372:Interferons / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011453:Prostaglandins / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D011453:Prostaglandins; D007372:Interferons