A.J. Carpenter

Invited review: Inflammation during the transition to lactation: New adventures with an old flame

For dairy cattle, the first several weeks of lactation represent the highest-risk period in their lives after their own neonatal period. Although more than 50% of cows during this period are estimated to suffer from at least one subclinical disorder, the complicated admixture of normal adaptations to lactation, infectious challenges, and metabolic disorders has made it difficult to determine which physiological processes are adaptive and which are pathological during this time. Subacute inflammation, a condition that has been well documented in obesity, has been a subject of great interest among dairy cattle physiologists in the past decade. Many studies have now clearly shown that essentially all cows experience some degree of systemic inflammation in the several days after parturition. The magnitude and likely persistence of the inflammatory state varies widely among cows, and several studies have linked the degree of postpartum inflammation to increased disease risk and decreased whole-lactation milk production. In addition to these associations, enhancing postpartum inflammation with repeated subacute administration of cytokines has impaired productivity and markers of health, whereas targeted use of nonsteroidal anti-inflammatory drugs during this window of time has enhanced whole-lactation productivity in several studies. Despite these findings, many questions remain about postpartum inflammation, including which organs are key initiators of this state and what signaling molecules are responsible for systemic and tissue-specific inflammatory states. Continued in vivo work should help clarify the degree to which mild postpartum inflammation is adaptive and whether the targeted use of anti-inflammatory drugs or nutrients can improve the health and productivity of dairy cows.

Holsteins Favor Heifers, Not Bulls: Biased Milk Production Programmed during Pregnancy as a Function of Fetal Sex

Mammalian females pay high energetic costs for reproduction, the greatest of which is imposed by lactation. The synthesis of milk requires, in part, the mobilization of bodily reserves to nourish developing young. Numerous hypotheses have been advanced to predict how mothers will differentially invest in sons and daughters, however few studies have addressed sex-biased milk synthesis. Here we leverage the dairy cow model to investigate such phenomena. Using 2.39 million lactation records from 1.49 million dairy cows, we demonstrate that the sex of the fetus influences the capacity of the mammary gland to synthesize milk during lactation. Cows favor daughters, producing significantly more milk for daughters than for sons across lactation. Using a sub-sample of this dataset (N = 113,750 subjects) we further demonstrate that the effects of fetal sex interact dynamically across parities, whereby the sex of the fetus being gestated can enhance or diminish the production of milk during an established lactation. Moreover the sex of the fetus gestated on the first parity has persistent consequences for milk synthesis on the subsequent parity. Specifically, gestation of a daughter on the first parity increases milk production by ∼445 kg over the first two lactations. Our results identify a dramatic and sustained programming of mammary function by offspring in utero. Nutritional and endocrine conditions in utero are known to have pronounced and long-term effects on progeny, but the ways in which the progeny has sustained physiological effects on the dam have received little attention to date.

Impact of oral meloxicam on circulating physiological biomarkers of stress and inflammation in beef steers after long distance transportation

Transportation stress can result in significant economic losses to producers due to decreased animal productivity and increased medication costs associated with sickness such as bovine respiratory disease (BRD). Meloxicam (MEL) provides pain relief and anti-inflammatory effects in cattle for several days after a single oral treatment. Our hypothesis was that MEL administration before shipping would reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef steers. Ninety-seven beef steers were blood sampled for baseline biomarker determination and then randomly assigned to receive either 1 mg/kg MEL (n = 49) or a placebo (CONT; n = 48) per os before a 1,316-km transportation event lasting approximately 16 h. Calves were then blood sampled on arrival and 5 d later. Changes in the hemogram, circulating plasma proteins, total carbon dioxide (TCO2), fibrinogen, substance P (SP), cortisol, haptoglobin (Hp)-matrix metalloproteinase-9 (MMP-9) complexes, and tumor necrosis factor α (TNFα) between treatments over time were compared using a mixed effects model with statistical significance designated as P < 0.05. Analysis of covariance was conducted to assess the relationship between circulating MEL concentrations and biomarker changes over time. An increase in neutrophil, platelet, monocyte, white blood cell, and red blood cell counts occurred after transportation (P < 0.0001) and a decrease in lymphocyte count were observed (P < 0.0001). Meloxicam treatment reduced the stress-induced neutrophilia (P = 0.0072) and circulating monocyte count (P = 0.013) on arrival. Mean corpuscle hemoglobin (P = 0.05), mean corpuscle volume (P = 0.05), and lymphocyte count (P = 0.05) were also greater in the CONT calves compared with MEL calves after transportation. Furthermore, Hp-MMP-9 complexes, TCO2, TNFα, plasma proteins, and SP increased and cortisol decreased after shipping (P < 0.01). Meloxicam treatment tended to reduce serum cortisol concentrations (P = 0.08) and there was evidence of a time × treatment interaction (P = 0.04). An inverse relationship between plasma MEL concentrations and circulation cortisol concentrations (P = 0.002) and neutrophil (P = 0.04) and basophil counts (P = 0.03) was also observed. The results suggest that MEL administration may reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef calves.

Analysis of rumen microbial populations in lactating dairy cattle fed diets varying in carbohydrate profiles and Saccharomyces cerevisiae fermentation product

The rumen microbial ecosystem is a critical factor that links diets to bovine physiology and productivity; however, information about dietary effects on microbial populations has generally been limited to small numbers of samples and qualitative assessment. To assess whether consistent shifts in microbial populations occur in response to common dietary manipulations in dairy cattle, samples of rumen contents were collected from 2 studies for analysis by quantitative real-time PCR (qPCR). In one study, lactating Holstein cows (n=8) were fed diets in which a nonforage fiber source replaced an increasing proportion of forages and concentrates in a 4×4 Latin square design, and samples of ruminal digesta were collected at 9-h intervals over 3 d at the end of each period. In the second study, lactating Holstein cows (n=15) were fed diets with or without the inclusion of a Saccharomyces cerevisiae fermentation product (SCFP) in a crossover design. In this study, rumen liquid and solid samples were collected during total rumen evacuations before and after feeding in a 42-h period. In total, 146 samples of ruminal digesta were used for microbial DNA isolation and analysis by qPCR. Validated primer sets were used to quantify total bacterial and anaerobic fungal populations as well as 12 well-studied bacterial taxa. The relative abundance of the target populations was similar to those previously reported. No significant treatment effects were observed for any target population. A significant interaction of treatment and dry matter intake was observed, however, for the abundance of Eubacterium ruminantium. Increasing dry matter intake was associated with a quadratic decrease in E. ruminantium populations in control animals but with a quadratic increase in E.ruminantium populations in cows fed SCFP. Analysis of sample time effects revealed that Fibrobacter succinogenes and fungal populations were more abundant postfeeding, whereas Ruminococcus albus tended to be more abundant prefeeding. Seven of the target taxa were more abundant in either the liquid or solid fractions of ruminal digesta. By accounting for the total mass of liquid and solid fractions in the rumen and the relative abundance of total bacteria in each fraction, it was estimated that 92% of total bacteria were found in the solid digesta fraction.

Hot topic: Early postpartum treatment of commercial dairy cows with nonsteroidal antiinflammatory drugs increases whole-lactation milk yield

Previous research has shown that postpartum administration of the nonsteroidal antiinflammatory drug (NSAID) sodium salicylate can increase 305-d milk yield in older dairy cattle (parity 3 and greater). However, in this prior work, sodium salicylate was delivered to cows via the drinking water, a method that does not align well with current grouping strategies on commercial dairy farms. The objective of the current study was to replicate these results on a commercial dairy farm with a simplified treatment protocol and to compare sodium salicylate with another NSAID, meloxicam. Dairy cattle in their second lactation and greater (n=51/treatment) were alternately assigned to 1 of 3 treatments at parturition, with treatments lasting for 3d. Experimental treatments began 12 to 36 h after parturition and were (1) 1 placebo bolus on the first day and 3 consecutive daily drenches of sodium salicylate (125 g/cow per day; SAL); (2) 1 bolus of meloxicam (675 mg/cow) and 3 drenches of an equal volume of water (MEL); or (3) 1 placebo bolus and 3 drenches of water (CON). Blood samples were collected on the first day of treatment, immediately following the last day of treatment, and 7d after the last day of treatment; plasma was analyzed for glucose, β-hydroxybutyrate (BHB), free fatty acids, haptoglobin, and paraoxonase. Milk production, body condition score, reproductive status, and retention in the herd were monitored for 365 d posttreatment, and effects of treatment, parity, days in milk, and interactions were evaluated in mixed effects models. Significance was declared at P<0.05. Whole-lactation milk and protein yields were greater in NSAID-treated cows, although 305-d fat production was not affected. There was a significant interaction of treatment and parity for plasma glucose concentration; MEL increased plasma glucose concentrations compared with CON and SAL in older cows. Sodium salicylate decreased plasma BHB concentration compared with MEL at 7d posttreatment, although no difference was detected immediately following treatment. Haptoglobin concentrations were elevated in SAL cows compared with CON. There was a tendency for CON cows to be removed from the herd more quickly than MEL cows (42 vs. 26% at 365 d posttreatment). Body condition score, concentrations of plasma free fatty acids and paraoxonase, and time to pregnancy were not affected by treatment. These results indicate that NSAID administration in postpartum cows has the potential to be a viable way to improve productivity and potentially longevity in commercial dairies, although further research is necessary to optimize recommendations for producers.

Effect of dietary sugar concentration and sunflower seed supplementation on lactation performance, ruminal fermentation, milk fatty acid profile, and blood metabolites of dairy cows

Previous research has shown that both sunflower seed (SF) and sucrose (SC) supplementation can result in variation in milk fat concentration and composition, possibly due to altered fermentation patterns and biohydrogenation of fatty acids in the rumen. The objective of this study was to determine the effects of different sugar concentrations with or without SF supplementation on lactation performance, ruminal fermentation, and milk fatty acid profile in lactating dairy cows. Eight multiparous Holstein dairy cows (body weight=620±15kg, 60±10 d in milk, mean ± standard deviation) were randomly assigned to treatments in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of treatments. Each 21-d period consisted of a 14-d diet adaptation period and 7-d collection period. Dairy cows were fed 1 of the following 4 diets: (1) no additional SC without SF supplementation (NSC-SF), (2) no additional SC with SF supplementation (NSC+SF), (3) SC without SF supplementation (SC-SF), and (4) SC with SF supplementation (SC+SF). The diets contained the same amount of forages (corn silage and alfalfa hay). Four isonitrogenous and isoenergetic diets were formulated by replacing corn grain with SC and SF and balanced using change in proportions of canola meal and sugar beet pulp. No interaction was detected between SC and SF supplementation with respect to dry matter intake, milk yield, and composition. A tendency was found for an interaction between inclusion of SC and SF on energy-corrected milk with the highest amount in the SC-SF diet. Ruminal pH and the molar proportion of acetate were affected by SC inclusion, with an increase related to the SC-SF diet. Diets containing SF decreased the concentrations of short-chain fatty acids (4:0 to 10:0) and medium-chain fatty acids (12:0 to 16:0) in milk fat. The addition of SC tended to decrease the concentration of total trans-18:1. These data provide evidence that exchanging SC for corn at 4% of dietary dry matter influenced milk fat content and rumen pH, resulting in a tendency for decreased concentration of trans-18:1 in milk fat. Sucrose alone did not alter the milk fatty acid profile when cows were fed a combination of unsaturated fat and sugar, although several significant interactions between sugar and unsaturated fat were observed.

Short communication: Sodium salicylate negatively affects rumen fermentation in vitro and in situ

Administration of sodium salicylate (SS) to cows in early lactation has a positive effect on whole-lactation milk production but a negative effect on metabolism in some cases. The objective of this trial was to determine whether SS directly affects rumen fermentation. Experiment 1 was designed to investigate the effects of direct inclusion of SS in a 24-h batch culture, and experiment 2 was designed to test the fermentative ability of rumen fluid from heifers who had received SS. In experiment 1, we combined strained and pooled rumen fluid from 3 heifers in a 2:1 ratio with McDougalls buffer, and added 150 mL of the inoculum to each flask (n = 5/treatment) with 2.5 g of fermentation substrate similar to a lactating cow ration, ground to 1 mm. We then added premixed treatments (1-mL volume) to achieve the desired final amount of SS (CON1 = 0 mg, LOW = 125 mg, MED = 250 mg, HI = 375 mg). In experiment 2, 6 heifers (n = 3/treatment) were drenched daily for 3 d, either with 62.5 g of SS dissolved in water (SAL) or an equal volume of water (CON2). Rumen fluid was collected from each heifer and was not pooled. After the fluid was mixed 2:1 with McDougalls buffer, 150 mL of inoculum was added to the fermentation flasks (n = 4/heifer) with 2.5 g of fermentation substrate. This experiment was performed the day before SS treatment began and repeated 1, 13, and 35 d after the end of the treatment period. We also performed an in situ experiment at each of these time points. In the first experiment, inclusion of SS resulted in a decrease in dry matter disappearance (DMD) over 24 h, as well as an increase in final pH. We detected no difference between treatments for gas production asymptotic volume, rate, or lag. In the second experiment, we detected a significant treatment × day interaction for DMD: we observed no difference between groups during a 24-h batch culture on the day following treatment, but SAL resulted in lower DMD on d 13 and d 35. We detected no treatment effect on the final pH of the batch culture or on any gas-production parameters. We observed a tendency for SAL to decrease the DMD rate in situ on the day after treatment. These results indicate that SS administration has a negative effect on rumen microorganisms.

Effects of early postpartum sodium salicylate treatment on long-term milk, intake, and blood parameters of dairy cows

Previous research has shown that cows who receive treatment with nonsteroidal anti-inflammatory drugs after calving may have increased milk yield beginning near peak lactation, resulting in greater 305-d milk production. It has not been demonstrated whether this response is associated with greater feed intake following the first 3 wk of lactation. Dry matter intake (DMI) and milk yield were measured daily for 56 cows over the first 120 d in milk. Cows in their second parity and greater were blocked by parity and alternately enrolled 12 to 36 h after calving into 1 of 2 treatments: either 3 daily drenches of water or 3 daily drenches of a similar volume of water containing 125 g of sodium salicylate (SAL) beginning 12 to 36 h after calving. Cows were housed in individual stalls to monitor DMI. Blood samples were collected before calving and on the last day of treatment, as well as at 7, 11, 14, 18, 21, 35, 49, 63, 77, 91, 105, and 120 d in milk. The SAL treatment did not affect estimated 305-d milk, fat, or protein yields (from monthly test days), daily milk yield or components, energy-corrected milk, fat-corrected milk, or DMI; however, an interaction between parity and treatment was observed for DMI, where second-parity SAL cows had decreased intake with no differences observed in older cows. This resulted in a parity by treatment interaction for the ratio of energy-corrected milk to DMI. Similarly, no main effects of treatment were observed for plasma glucose, β-hydroxybutyrate (BHB), or fatty acid concentrations, but we noted interactions between treatment and parity for glucose, BHB, and insulin. Older cows had greater plasma glucose and insulin concentrations and decreased plasma BHB following SAL but no differences were observed in second parity animals. Alterations in glucose and insulin resulted in a tendency for a treatment by time interaction for the revised quantitative insulin sensitivity check index. Feeding behavior was also altered following SAL administration, resulting in fewer but longer meals, as well as a tendency for greater meal weight. A tendency for a treatment by week interaction for inter-meal interval was observed, as well as a parity by treatment interaction for meal weight. Despite the lack of a milk yield response, SAL had a prolonged programming effect on feeding behavior and blood variables over the first 120 DIM, with responses largely dependent on parity.

Effects of postpartum treatment with non-steroidal anti-inflammatory drugs on milk production and culling risk in dairy cattle

Inflammation during early lactation is common in dairy cattle, and a high degree of inflammation during this time has recently been associated with both lower productivity and greater risk of disease during that lactation. Early lactation treatments with two non-steroidal anti-inflammatory drugs were compared with a placebo treatment to evaluate effects on whole-lactation productivity and retention in the herd. Both meloxicam and sodium salicylate increased whole-lactation milk and milk protein yields by 6 to 9%, despite being administered for only 1 or 3 days in early lactation, respectively. In addition, meloxicam treatment tended to decrease the risk of cows leaving the herd during the lactation. These results indicate that postpartum inflammatory signals have long-lasting effects on lactation in dairy cattle.