Cows selected for divergent mastitis susceptibility display a differential liver transcriptome profile after experimental Staphylococcus aureus mammary gland inoculation.

Infection and inflammation of the mammary gland, and especially prevention of mastitis, are still major challenges for the dairy industry. Different approaches have been tried to reduce the incidence of mastitis. Genetic selection of cows with lower susceptibility to mastitis promises sustainable success in this regard. Bos taurus autosome (BTA) 18, particularly the region between 43 and 59 Mb, harbors quantitative trait loci (QTL) for somatic cell score, a surrogate trait for mastitis susceptibility. Scrutinizing the molecular bases hereof, we challenged udders from half-sib heifers having inherited either favorable paternal haplotypes for somatic cell score (Q) or unfavorable haplotypes (q) with the Staphylococcus aureus pathogen. RNA sequencing was used for an in-depth analysis of challenge-related alterations in the hepatic transcriptome. Liver exerts highly relevant immune functions aside from being the key metabolic organ. Hence, a holistic approach focusing on the liver enabled us to identify challenge-related and genotype-dependent differentially expressed genes and underlying regulatory networks. In response to the S. aureus challenge, we found that heifers with Q haplotypes displayed more activated immune genes and pathways after S. aureus challenge compared with their q half-sibs. Furthermore, we found a significant enrichment of differentially expressed loci in the genomic target region on BTA18, suggesting the existence of a regionally acting regulatory element with effects on a variety of genes in this region.

In vivo model to study the impact of genetic variation on clinical outcome of mastitis in uniparous dairy cows.

BACKGROUND: In dairy herds, mastitis causes detrimental economic losses. Genetic selection offers a sustainable tool to select animals with reduced susceptibility towards postpartum diseases. Studying underlying mechanisms is important to assess the physiological processes that cause differences between selected haplotypes. Therefore, the objective of this study was to establish an in vivo infection model to study the impact of selecting for alternative paternal haplotypes in a particular genomic region on cattle chromosome 18 for mastitis susceptibility under defined conditions in uniparous dairy cows. RESULTS: At the start of pathogen challenge, no significant differences between the favorable (Q) and unfavorable (q) haplotypes were detected. Intramammary infection (IMI) with Staphylococcus aureus 1027 (S. aureus, n = 24, 96 h) or Escherichia coli 1303 (E. coli, n = 12, 24 h) was successfully induced in all uniparous cows. This finding was confirmed by clinical signs of mastitis and repeated recovery of the respective pathogen from milk samples of challenged quarters in each animal. After S. aureus challenge, Q-uniparous cows showed lower somatic cell counts 24 h and 36 h after challenge (P < 0.05), lower bacterial shedding in milk 12 h after challenge (P < 0.01) and a minor decrease in total milk yield 12 h and 24 h after challenge (P < 0.01) compared to q-uniparous cows. CONCLUSION: An in vivo infection model to study the impact of genetic selection for mastitis susceptibility under defined conditions in uniparous dairy cows was successfully established and revealed significant differences between the two genetically selected haplotype groups. This result might explain their differences in susceptibility towards IMI. These clinical findings form the basis for further in-depth molecular analysis to clarify the underlying genetic mechanisms for mastitis resistance.

Genetic selection for bovine chromosome 18 haplotypes associated with divergent somatic cell score affects postpartum reproductive and metabolic performance.

The susceptibility of animals to periparturient diseases has a great effect on the economic efficiency of dairy industries, on the frequency of antibiotic treatment, and on animal welfare. The use of selection for breeding cows with reduced susceptibility to diseases offers a sustainable tool to improve dairy cattle farming. Several studies have focused on the association of distinct bovine chromosome 18 genotypes or haplotypes with performance traits. The aim of this study was to test whether selection of Holstein Friesian heifers via SNP genotyping for alternative paternal chromosome 18 haplotypes associated with favorable (Q) or unfavorable (q) somatic cell scores influences postpartum reproductive and metabolic diseases. Thirty-six heifers (18 Q and 18 q) were monitored from 3 wk before calving until necropsy on d 39 (± 4 d) after calving. Health status and rectal temperature were measured daily, and body condition score and body weight were assessed once per week. Blood samples were drawn twice weekly, and levels of insulin, nonesterified fatty acids, insulin-like growth factor-I, growth hormone, and ß-hydroxybutyrate were measured. Comparisons between the groups were performed using Fisher's exact test, chi-squared test, and the GLIMMIX procedure in SAS. Results showed that Q-heifers had reduced incidence of metritis compared with q-heifers and were less likely to develop fever. Serum concentrations of ß-hydroxybutyrate were lower and insulin-like growth factor-I plasma concentrations were higher in Q- compared with q-heifers. However, the body condition score and withers height were comparable between haplotypes, but weight loss tended to be lower in Q-heifers compared with q-heifers. No differences between the groups were detected concerning retained fetal membranes, uterine involution, or onset of cyclicity. In conclusion, selection of chromosome 18 haplotypes associated with a reduced somatic cell score resulted in a decreased incidence of postpartum reproductive and metabolic diseases in this study. The presented data add to the existing knowledge aimed at avoiding negative consequences of genetic selection strategies in dairy cattle farming. The underlying causal mechanisms modulated by haplotypes in the targeted genomic region and immune competence necessitate further investigation.

Correction to: Characterization of functional traits with focus on udder health in heifers with divergent paternally inherited haplotypes on BTA18.

The original article [1] contained an error whereby the captions to Figs 2 and 3 were mistakenly inverted; this has now been corrected.

Characterization of functional traits with focus on udder health in heifers with divergent paternally inherited haplotypes on BTA18.

BACKGROUND: A major challenge in modern medicine and animal husbandry is the issue of antimicrobial resistance. One approach to solving this potential medical hazard is the selection of farm animals with less susceptibility to infectious diseases. Recent advances in functional genome analysis and quantitative genetics have opened the horizon to apply genetic marker information for efficiently identifying animals with preferential predisposition regarding health traits. The current study characterizes functional traits with a focus on udder health in dairy heifers. The animals were selected for having inherited alternative paternal haplotypes for a genomic region on Bos taurus chromosome (BTA) 18 genetically associated with divergent susceptibility to longevity and animal health, particularly mastitis. RESULTS: In the first weeks of lactation, the q heifers which had inherited the unfavorable (q) paternal haplotype displayed a significantly higher number of udder quarters with very low somatic cell count (< 10,000 cells / ml) compared to their paternal half-sib sisters with the favorable (Q) paternal haplotype. This might result in impaired mammary gland sentinel function towards invading pathogens. Furthermore, across the course of the first lactation, there was indication that q half-sib heifers showed higher somatic cell counts, a surrogate trait for udder health, in whole milkings compared to their paternal half-sib sisters with the favorable (Q) paternal haplotype. Moreover, heifers with the haplotype Q had a higher feed intake and higher milk yield compared to those with the q haplotype. Results of this study indicate that differences in milk production and calculated energy balance per se are not the main drivers of the genetically determined differences between the BTA18 Q and q groups of heifers. CONCLUSIONS: The paternally inherited haplotype from a targeted BTA18 genomic region affect somatic cell count in udder quarters during the early postpartum period and might also contribute to further aspects of animal's health and performance traits due to indirect effects on feed intake and metabolism.

Thyroid hormone profiles and TSH evaluation during early pregnancy and the transition period in dairy cows.

The thyroid hormone axis is one important endocrine system within a complex system of various factors and hormones necessary to establish and maintain pregnancy in cattle and in metabolic adaptations towards lactation. Pregnancy and lactation occur contemporaneously in dairy cows, and have major impacts on thyroid hormones as well as status of the hypothalamus-pituitary thyroid axis influences pregnancy and lactation. As especially the thyroid hormone axis with special focus to TSH is not well studies in the past, the aim of the study was to examine the thyroid hormone axis, especially in heifers during adaptation to the first lactation, to verify the association between lactation and thyroid hormones. Secondly, the early pregnancy period was the focus of the present investigation. To determine thyroid hormone patterns and especially thyroid-stimulating hormone (TSH) during the transition period, 12 primiparous Holstein Friesian cows and 41 pregnant and 34 non-pregnant pluriparous cows were sampled. During the transition period, thyroxin (T4) concentrations decreased after calving in primiparous cows, and the milk yield [kg] was negatively correlated with triiodothyronine (T3) and T4 concentrations. In pregnant and non-pregnant pluriparous cows, T3, T4, TSH and free T4 (fT4) decreased between the day of ovulation (day 0) and day 18. From day 18 of gestation to day 100 after AI, an increase in TSH and fT4 and a decrease in Reverse T3 (rT3) was observed in the pregnant cows. In conclusion, the results of the present study confirm that regulative processes within the thyroid hormone metabolism occur during early lactation. For the first time it could be shown in dairy cows that TSH and fT4 increased during early pregnancy whereas rT3 decreased indicating also in bovine species a TSH stimulatory effect by pregnancy.

Pregnancy-Induced ISG-15 and MX-1 Gene Expression is Detected in the Liver of Holstein-Friesian Heifers During Late Peri-Implantation Period.

The bovine embryonic signal interferon-τ (IFN-τ) produced by the trophoblast is known to pass through the uterine fluid towards the endometrium and further into the maternal blood, where IFN-τ induces specific expression of interferon-stimulated gene expression (ISG), for example in peripheral leucocytes. In sheep, it was shown experimentally by administration of IFN-τ that ISG is also detectable in the liver. The objective was to test whether ISG can be detected in liver biopsy specimens from Holstein-Friesian heifers during early pregnancy. Liver biopsies were taken on day 18 from pregnant and non-pregnant heifers (n = 19), and the interferon-stimulated protein 15 kDa (ISG-15) and myxovirus-resistance protein-1 (MX-1) gene expression was detected. The expression of both MX-1 (p: 24.33 ± 7.40 vs np: 9.00 ± 4.02) and ISG-15 (p: 43.73 ± 23.22 vs 7.83 ± 3.63) was higher in pregnant compared to non-pregnant heifers (p < 0.05). In conclusion, pregnancy induced ISG-15 and MX-1 gene expression in the liver already at day 18 in cattle.