title: Relationships between Circulating Urea Concentrations and Endometrial Function in Postpartum Dairy Cows.
abstract: Both high and low circulating urea concentrations, a product of protein metabolism, are associated with decreased fertility in dairy cows through poorly defined mechanisms. The rate of involution and the endometrial ability to mount an adequate innate immune response after calving are both critical for subsequent fertility. Study 1 used microarray analysis to identify genes whose endometrial expression 2 weeks postpartum correlated significantly with the mean plasma urea per cow, ranging from 3.2 to 6.6 mmol/L. The biological functions of 781 mapped genes were analysed using Ingenuity Pathway Analysis. These were predominantly associated with tissue turnover (e.g., BRINP1, FOXG1), immune function (e.g., IL17RB, CRISPLD2), inflammation (e.g., C3, SERPINF1, SERPINF2) and lipid metabolism (e.g., SCAP, ACBD5, SLC10A). Study 2 investigated the relationship between urea concentration and expression of 6 candidate genes (S100A8, HSP5A, IGF1R, IL17RB, BRINP1, CRISPLD2) in bovine endometrial cell culture. These were treated with 0, 2.5, 5.0 or 7.5 mmol/L urea, equivalent to low, medium and high circulating values with or without challenge by bacterial lipopolysaccharide (LPS). LPS increased S100A8 expression as expected but urea treatment had no effect on expression of any tested gene. Examination of the genes/pathways involved suggests that plasma urea levels may reflect variations in lipid metabolism. Our results suggest that it is the effects of lipid metabolism rather than the urea concentration which probably alter the rate of involution and innate immune response, in turn influencing subsequent fertility.
authors.affiliation: Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, UK. zcheng@rvc.ac.uk.
authors.forename: Zhangrui
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, UK. coguejiofor@rvc.ac.uk.
authors.forename: Chike F
authors.initials: CF
authors.lastname: Oguejiofor
authors.affiliation: Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, UK. theerawat.s@chula.ac.th.
authors.forename: Theerawat
authors.initials: T
authors.lastname: Swangchan-Uthai
authors.affiliation: Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, UK. scarr@rvc.ac.uk.
authors.forename: Susan
authors.initials: S
authors.lastname: Carr
authors.affiliation: Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire AL9 7TA, UK. dcwathes@rvc.ac.uk.
authors.forename: D Claire
authors.initials: DC
authors.lastname: Wathes
keywords: cholesterol; endometrium; innate immunity; involution; protein metabolism