Relationships between Circulating Urea Concentrations and Endometrial Function in Postpartum Dairy Cows

Abstract

Simple SummaryDairy cows fed high levels of protein to increase milk yield tend to have reduced fertility but the reasons behind this are unclear. Differing dietary protein levels are reflected in altered urea concentrations in both blood and other tissues including the uterus. We showed that the circulating urea concentration was highly correlated to changed expression levels of many genes in the endometrium shortly after calving. These were predominantly associated with tissue repair, innate immunity and lipid metabolism. A subsequent study found no effect of altered urea concentration on endometrial gene expression in vitro implying that the dietary influence is indirect.AbstractBoth 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.

Impact of short nutrient stimuli with different energy source on follicle dynamics and quality of oocyte from hormonally stimulated goats

“…The levels of nutrients and metabolites under conditions that induce a negative energy balance act on the hypothalamic pathway, reducing gonadotrophin‐releasing hormone secretion (GnRH) and consequent luteinizing hormone (LH) peak deficiency, interfering with follicular development (Scaramuzzi et al, , ). In addition, these levels alter the microenvironment for ovarian follicular development due to changes in cholesterol and free fatty acid levels, affecting essential functions in membrane biogenesis (Renaville et al, ), signalling process (McKeegan & Sturmey, ) and formation of steroids and prostaglandins, essential for reproductive function (Cheng, Oguejiofor, Swangchan‐Uthai, Carr, & Wathes, ). These energy changes mediate a range of cellular actions, such as in intracellular signalling cascades (Leese & Brison, ), which may alter the functioning of cytoplasmic organelles such as mitochondria in oocytes and zygotes (Igosheva et al, ), modifying the levels of mRNAs that code for lactate dehydrogenase A (LDHA) and glyceraldehyde 3‐phosphate dehydrogenase (GAPDH), both linked to energy metabolism and involved in glycolysis and cytosolic reduction (Van Hoeck et al, ).…”

Transition Period of the Dairy Cow Revisited: II. Homeorhetic Stimulus and Ketosis With Implication for Fertility

“…Uncoupling of the GH-IGF-1 axis: Ketotic cows exhibit, in addition to the discussed metabolic and hormonal changes, an uncoupling of the GH-IGF-1 axis (Du et al, 2018): an increase of GH and a decrease of IGF-1. Furthermore, in calf liver cells in vitro, NEFA or BHB causes a reduction of GHR 1A and IGF-1 mRNA expression (uncoupling of GH-IGF-1 axis) (Du et al, 2018) and explains the earlier observation of a negative correlation between NEFA as well as BHB and IGF-1 concentrations (Wathes et al, 2007;Cheng et al, 2015).…”

Biochemical analysis of uterine fluid for identification of indicators for subclinical endometritis in the water buffalo (Bubalus bubalis)

“…Although urea and urea N concentrations have not been studied in relation to uterine infection, the existing information suggests that elevated levels of urea and urea N are associated with reduced reproductive efficiency in cows (Butler, Calaman, & Beam, ; Ferguson, Galligan, Blanchard, & Reeves, ; Hammon, Holyoak, & Dhiman, ; Melendez, Donovan, & Hernandez, ; Rajala‐Schultz, Saville, Frazer, & Wittum, ). Recently, Cheng, Chike, Uthai, Carr, and Wathes () indicated a negative relationship between urea concentrations and expression of genes associated with innate immunity and inflammation in the cow uterus. In case of uterine infection, the innate immune system plays an important role in the elimination of uterine pathogens.…”