Comparison of the effects of high and low milk-replacer feeding regimens on health and growth of crossbred dairy heifers

Context: Pre-weaning growth in dairy heifers is highly dependent on the amount of milk fed. Both milk replacer (MR) and associated labour are costly, encouraging restricted milk rations and once-a-day feeding. Aims: This study compared performance relating to the growth and health of calves receiving one of two commercial feeding regimens: High or Low. Methods: All heifers born during the Spring (January–March) calving block on a commercial UK farm with mixed-breed genetics were recruited at birth, randomly assigned to the High (n = 104, receiving MR-A) or Low (n = 88, receiving MR-B) feed group and reared indoors on straw bedding, with free access to concentrate. Both groups initially received MR twice daily. The High group continued to receive MR twice daily throughout the experiment, whereas the Low group calves were reduced to a single MR feed daily during Weeks 4–8. Blood samples were taken in Weeks 1 and 6 to assess passive transfer and measure circulating insulin-like growth factor 1 (IGF1). The Wisconsin calf-scoring system was used to assess health of calves in Weeks 1, 2, 4, 6 and 8 and at 6 months and size was also measured at these times. Data were analysed by univariate and multivariate models. Key results: Passive transfer was good in both groups (serum total protein (mean ± s.d.) 60.9 ± 9.1 mg/mL) with no differences in pre-weaning disease incidence; diarrhoea occurred in 64.5% and bovine respiratory disease in 26.3% of calves. High group calves were significantly heavier, taller and longer at all pre-weaning examinations except recruitment owing to more growth in the first month, and remained significantly larger at 6 months: weight 157 ± 8 vs 149 ± 7 kg, height 103 ± 5 vs 100 ± 5 cm, length 90 ± 4 vs 88 ± 5 cm. Plasma IGF1 concentrations at around Week 6 were doubled in the High group (101 ± 38.6 vs 55 ± 34.1 ng/mL). Bovine respiratory disease was associated with reduced weight gain. Heifers with diarrhoea were leaner at weaning. High feed group, weight at recruitment and good passive transfer were positively associated with weight at 6 months. Conclusions: Higher feeding levels pre-weaning increased growth rates and IGF1, although the disease incidence was unaffected. Implications: Previous studies have shown that more growth and higher IGF1 pre-weaning are associated with a lower age at first calving and an increased chance of reaching the end of first lactation. These in turn improve long-term performance

Combining Genome Wide Association Studies and Differential Gene Expression Data Analyses Identifies Candidate Genes Affecting Mastitis Caused by Two Different Pathogens in the Dairy Cow

Mastitis is a costly disease which hampers the dairy industry. Inflammation of the mammary gland is commonly caused by bacterial infection, mainly Escherichia coli, Streptococcus uberis and Staphylococcus aureus. As more bacteria become multi-drug resistant, one potential approach to reduce the disease incidence rate is to breed selectively for the most appropriate and potentially protective innate immune response. The genetic contribution to effective disease resistance is, however, difficult to identify due to the complex interactions that occur. In the present study two published datasets were searched for common differentially expressed genes (DEGs) with similar changes in expression in mammary tissue following intra-mammary challenge with either E. coli or S. uberis. Additionally, the results of seven published genome-wide association studies (GWAS) on different dairy cow populations were used to compile a list of SNPs associated with somatic cell count. All genes located within 2 Mbp of significant SNPs were retrieved from the Ensembl database, based on the UMD3.1 assembly. A final list of 48 candidate genes with a role in the innate immune response identified from both the DEG and GWAS studies was further analyzed using Ingenuity Pathway Analysis. The main signalling pathways highlighted in the response of the bovine mammary gland to both bacterial infections were 1) granulocyte adhesion and diapedesis, 2) ephrin receptor signalling, 3) RhoA signalling and 4) LPS/IL1 mediated inhibition of RXR function. These pathways comprised a network regulating the activity of leukocytes, especially neutrophils, during mammary gland inflammation. The timely and properly controlled movement of leukocytes to infection loci seems particularly important in achieving a good balance between pathogen elimination and excessive tissue damage. These results suggest that polymorphisms in key genes in these pathways such as SELP, SELL, BCAR1, ACTR3, CXCL2, CXCL6, CXCL8 and FABP may influence the ability of dairy cows to resist mastitis

Global Transcriptomic Profiling of Bovine Endometrial Immune Response In Vitro. I. Effect of Lipopolysaccharide on Innate Immunity

The dysregulation of endometrial immune response to bacterial lipopolysaccharide (LPS) has been implicated in uterine disease and infertility in the postpartum dairy cow, although the mechanisms are not clear. Here, we investigated whole-transcriptomic gene expression in primary cultures of mixed bovine epithelial and stromal endometrial cells. Cultures were exposed to LPS for 6 h, and cellular response was measured by bovine microarray. Approximately 30% of the 1006 genes altered by LPS were classified as being involved in immune response. Cytokines and chemokines (IL1A, CX3CL1, CXCL2, and CCL5), interferon (IFN)-stimulated genes (RSAD2, MX2, OAS1, ISG15, and BST2), and the acute phase molecule SAA3 were the most up-regulated genes. Ingenuity Pathway Analysis identified up-regulation of many inflammatory cytokines and chemokines, which function to attract immune cells to the endometrium, together with vascular adhesion molecules and matrix metalloproteinases, which can facilitate immune cell migration from the tissue toward the uterine lumen. Increased expression of many IFN-signaling genes, immunoproteasomes, guanylate-binding proteins, and genes involved in the intracellular recognition of pathogens suggests important roles for these molecules in the innate defense against bacterial infections. Our findings confirmed the important role of endometrial cells in uterine innate immunity, whereas the global approach used identified several novel immune response pathways triggered by LPS in the endometrium. Additionally, many genes involved in endometrial response to the conceptus in early pregnancy were also altered by LPS, suggesting one mechanism whereby an ongoing response to infection may interfere with the establishment of pregnancy

Acute BVDV infection inhibits expression of interferon-stimulated genes during pregnancy recognition in bovine endometrium

Bovine viral diarrhea virus (BVDV) can evade host detection by downregulation of interferon signaling pathways. Infection of cows with noncytopathic (ncp) BVDV can cause early embryonic mortality. Upregulation of type I interferon stimulated genes (ISGs) by blastocyst-secreted interferon tau (IFNT) is a crucial component of the maternal recognition of pregnancy (MRP) in ruminants. This study investigated the potential of acute BVDV infection to disrupt MRP by modulating endometrial ISG expression. Endometrial cells from 10 BVDV-free cows were cultured and treated with 0 or 100 ng/ml IFNT for 24 h in the absence or presence of ncpBVDV infection to yield four treatment groups: CONT, ncpBVDV, IFNT, or ncpBVDV+IFNT. ncpBVDV infection alone only upregulated TRIM56, but reduced mRNA expression of ISG15, MX2, BST2, and the proinflammatory cytokine IL1B. As anticipated, IFNT treatment alone significantly increased expression of all 17 ISGs tested. In contrast to the limited effect of ncpBVDV alone, the virus markedly inhibited IFNT-stimulated expression of 15 ISGs tested (ISG15, HERC5, USP18, DDX58, IFIH1, IFIT1, IFIT3, BST2, MX1, MX2, RSAD2, OAS1Y, SAMD9, GBP4, and PLAC8), together with ISG15 secreted protein. Only TRIM56 and IFI27 expression was unaltered. IL1B expression was reduced by the combined treatment. These results indicate that acute ncpBVDV infection may decrease uterine immunity and lead to MRP failure through inhibition of IFNT-stimulated endometrial ISG production. This in turn could reduce fertility and predispose cows to uterine disease, while evasion of the normal uterine immune response by ncpBVDV may contribute to maintenance and spreading of this economically important disease

Global Transcriptomic Profiling of Bovine Endometrial Immune Response In Vitro. II. Effect of Bovine Viral Diarrhea Virus on the Endometrial Response to Lipopolysaccharide

Infection with noncytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS). Primary cultures of mixed epithelial and stromal cells were divided into four treatment groups (control [CONT], BVDV, CONT+LPS, and BVDV+LPS) and infected with ncpBVDV for 4 days followed by treatment with LPS for 6 h. Whole-transcriptomic gene expression was measured followed by Ingenuity Pathway Analysis. Differential expression of 184 genes was found between CONT and BVDV treatments, showing interplay between induction and inhibition of responses. Up-regulation of TLR3, complement, and chemotactic and TRIM factors by ncpBVDV all suggested an ongoing immune response to viral infection. Down-regulation of inflammatory cytokines, chemokines, CXCR4, and serine proteinase inhibitors suggested mechanisms by which ncpBVDV may simultaneously counter the host response. Comparison between BVDV+LPS and CONT+LPS treatments showed 218 differentially expressed genes. Canonical pathway analysis identified the key importance of interferon signaling. Top down-regulated genes were RSAD2, ISG15, BST2, MX2, OAS1, USP18, IFIT3, IFI27, SAMD9, IFIT1, and DDX58, whereas TRIM56, C3, and OLFML1 were most up-regulated. Many of these genes are also regulated by IFNT during maternal recognition of pregnancy. Many innate immune genes that typically respond to LPS were inhibited by ncpBVDV, including those involved in pathogen recognition, inflammation, interferon response, chemokines, tissue remodeling, cell migration, and cell death/survival. Infection with ncpBVDV can thus compromise immune function and pregnancy recognition, thereby potentially predisposing infected cows to postpartum bacterial endometritis and reduced fertility

A mechanistic inter-species comparison of flicker sensitivity

AbstractThe general validity of both the Rovamo [Vision Res. 39 (1999) 533] and Barten (Contrast sensitivity of the human eye, SPIE Optical Engineering Press, 1999), modulation transfer function models for describing flicker sensitivity in vertebrates was examined using published data for goldfish, chickens, tree shrews, ground squirrels, cats, pigeons and humans. Both models adequately described the flicker response in each species at frequencies greater than approximately 1 Hz. At lower frequencies, response predictions differed between the two models and this was due, in part, to dissimilar definitions of the role played by lateral inhibition in the retina. Modelled flicker sensitivity for a matched retinal illuminance condition enabled a direct inter-species comparison of signal processing response times at the photoreceptor level. The modelled results also quantified differences between species in post-retinal signal processing capability. Finally, the relationship between flicker frequency response curves and the perception of temporal signals in real visual scenes was examined for each species. It is proposed that the area under the flicker sensitivity function may offer a single “figure of merit” for specifying overall sensitivity to time signals in a species’ environment

Importance of Viral Disease in Dairy Cow Fertility

Many viral diseases are endemic in cattle populations worldwide. The ability of many viruses to cross the placenta and cause abortions and fetal malformations is well understood. There is also significant evidence that viral infections have additional actions in dairy cows, which are reflected in reduced conception rates. These effects are, however, highly dependent on the time at which an individual animal first contracts the disease and are less easy to quantify. This paper reviews the evidence relating to five viruses that can affect fertility, together with their potential mechanisms of action. Acute infection with non-cytopathic bovine viral diarrhea virus (BVDV) in mid-gestation increases abortion rates or causes the birth of persistently infected calves. BVDV infections closer to the time of breeding can have direct effects on the ovaries and uterine endometrium, which cause estrous cycle irregularities and early embryo mortality. Fertility may also be reduced by BVDV-induced immunosuppression, which increases the susceptibility to bacterial infections. Bovine herpesvirus (BHV)-1 is most common in pre-pubertal heifers, and can slow their growth, delay breeding, and increase the age at first calving. Previously infected animals subsequently show reduced fertility. Although this may be associated with lung damage, ovarian lesions have also been reported. Both BHV-1 and BHV-4 remain latent in the host following initial infection and may be reactivated later by stress, for example associated with calving and early lactation. While BHV-4 infection alone may not reduce fertility, it appears to act as a co-factor with established bacterial pathogens such as Escherichia coli and Trueperella pyogenes to promote the development of endometritis and delay uterine repair mechanisms after calving. Both Schmallenberg virus (SBV) and bluetongue virus (BTV) are transmitted by insect vectors and lead to increased abortion rates and congenital malformations. BTV-8 also impairs the development of hatched blastocysts; furthermore, infection around the time of breeding with either virus appears to reduce conception rates. Although the reductions in conception rates are often difficult to quantify, they are nevertheless sufficient to cause economic losses, which help to justify the benefits of vaccination and eradication schemes

Mechanisms linking bovine viral diarrhea virus (BVDV) infection with infertility in cattle

Bovine viral diarrhea virus (BVDV) is an important infectious disease agent that causes significant reproductive and economic losses in the cattle industry worldwide. Although BVDV infection is known to cause poor fertility in cattle, a greater part of the underlying mechanisms particularly associated with early reproductive losses are not clearly understood. Previous studies reported viral compromise of reproductive function in infected bulls. In females, BVDV infection is thought to be capable of killing the oocyte, embryo or fetus directly, or to induce lesions that result in fetal abortion or malformation. BVDV infections may also induce immune dysfunction, and predispose cattle to other diseases that cause poor health and fertility. Other reports also suggested BVDV-induced disruption of the reproductive endocrine system, and a disruption of leukocyte and cytokine functions in the reproductive organs. More recent studies have provided evidence of viral-induced suppression of endometrial innate immunity that may predispose to uterine disease. Furthermore, there is new evidence that BVDV may potentially disrupt the maternal recognition of pregnancy or the immune protection of the conceptus. This review brings together the previous reports with the more recent findings, and attempts to explain some of the mechanisms linking this important virus to infertility in cattle

Association between Single Nucleotide Polymorphism in RelA with Somatic Cell Count and Longevity Supports Importance of NF-¦ÊB Signalling in Cattle Health

Mastitis reduces milk production and causes culling. The NF-κB transcription factor RelA plays a central regulatory role in innate immunity. This study used a candidate gene approach to investigate associations between the synonymous C/G SNP rs48035703 in RELA with somatic cell count (SCC) and survival time. Blood samples were collected from 337 Holstein-Friesian heifers on 19 farms and genotyped by PCR-restriction fragment length polymorphism. Animals were monitored from 6 months until 2340 d of age. Pedigree, milk production and disease records were obtained. Genotype frequencies were CC 0.63, CG 0.30 and GG 0.06. The C allele had a favourable additive effect on survival: average longevities from birth were CC, 1872 d; CG, 1745 d and GG 1596 d (P < 0.003). Log transformed first lactation somatic cell count (SCC)data showed a significant association with this SNP using an allele substitution model (mean residuals ± SD: GG 0.30 ± 1.263; CG 0.22 ± 0.994, CC −0.04 ± 0.803, P < 0.05). More CC cows than expected were classified as intermediate and fewer as mastitic (30.4% v 45.9%) with respect to SCC class when categorised as 0 (unaffected), 1 (intermediate) and 2 (mastitic), whereas for CG heterozygotes fewer were intermediate and more were mastitic (12.1% v 60.3%) (p = 0.05). RELA rs48035703 CC genotype cows were therefore less likely to experience a high SCC and survived longer. These results support a role for RelA in combating mammary gland infection and warrant further studies in additional populations

Bovine Endometrial Cells Mount Innate Immune Response to the Intracellular Ligands CL097 and Poly(dA:dT) Indicating Roles against Uterine Viruses

Uterine infection and endometritis cause infertility and economic losses in the cattle industry. The innate immune response of the endometrium is critical in the elimination of pathogenic organisms that invade the uterus in postpartum cows. This study investigated the response of bovine endometrium to synthetic intracellular ligands which activate innate immunity by stimulating similar receptors to those used to recognise the presence of some viruses. Mixed primary epithelial and stromal cell cultures were treated with 5 μg/ml of CL097 (a TLR7/8 ligand) or 2 μg/ml of poly(dA:dT) (a DNA analogue) for either 6 h or 24 h. Cellular responses were assessed by the mRNA expression of 18 immune-related genes and 3 endogenous reference genes by conventional PCR followed by qRT-PCR from four replicate experiments. Bovine endometrial cells expressed the cytosolic pattern recognition receptors (PRRs) DDX58 (RIG-I), IFIH1 (MDA5) and LRRFIP1 which act as intracellular nucleic acid sensors. Neither ligand altered the expression of the extra-cytosolic pattern recognition receptors (PRRs) TLR3, TLR4, TLR7 or TLR8 whereas poly(dA:dT) treatment increased the expression of IFIH1 and DDX58. Treated cells also responded to CL097 or poly(dA:dT) with a differential up-regulation of genes involved in innate immune response including type I interferon/antiviral response (MX1, IFNAR1), antimicrobial activity (MUC1, SLPI) and cytokine activity (TNF, IL1B, IL8). Bovine endometrial cells therefore express both cytosolic and extra-cytosolic intracellular PRRs and are able to mount an innate immune response upon stimulation with intracellular ligands. This suggests an important role for these cells in the defence against viruses that may be present in the uterus in postpartum cows