Genome-wide association study of age at puberty and its (co)variances with fertility and stature in growing and lactating Holstein-Friesian dairy cattle.

Reproductive performance is a key determinant of cow longevity in a pasture-based, seasonal dairy system. Unfortunately, direct fertility phenotypes such as intercalving interval or pregnancy rate tend to have low heritabilities and occur relatively late in an animal's life. In contrast, age at puberty (AGEP) is a moderately heritable, early-in-life trait that may be estimated using an animal's age at first measured elevation in blood plasma progesterone (AGEP4) concentrations. Understanding the genetic architecture of AGEP4 in addition to genetic relationships between AGEP4 and fertility traits in lactating cows is important, as is its relationship with body size in the growing animal. Thus, the objectives of this research were 3-fold. First, to estimate the genetic and phenotypic (co)variances between AGEP4 and subsequent fertility during first and second lactations. Second, to quantify the associations between AGEP4 and height, length, and BW measured when animals were approximately 11 mo old (standard deviation = 0.5). Third, to identify genomic regions that are likely to be associated with variation in AGEP4. We measured AGEP4, height, length, and BW in approximately 5,000 Holstein-Friesian or Holstein-Friesian × Jersey crossbred yearling heifers across 54 pasture-based herds managed in seasonal calving farm systems. We also obtained calving rate (CR42, success or failure to calve within the first 42 d of the seasonal calving period), breeding rate (PB21, success or failure to be presented for breeding within the first 21 d of the seasonal breeding period) and pregnancy rate (PR42, success or failure to become pregnant within the first 42 d of the seasonal breeding period) phenotypes from their first and second lactations. The animals were genotyped using the Weatherby's Versa 50K SNP array (Illumina, San Diego, CA). The estimated heritabilities of AGEP4, height, length, and BW were 0.34 (90% credibility interval [CRI]: 0.30, 0.37), 0.28 (90% CRI: 0.25, 0.31), 0.21 (90% CRI: 0.18, 0.23), and 0.33 (90% CRI: 0.30, 0.36), respectively. In contrast, the heritabilities of CR42, PB21 and PR42 were all <0.05 in both first and second lactations. The genetic correlations between AGEP4 and these fertility traits were generally moderate, ranging from 0.11 to 0.60, whereas genetic correlations between AGEP4 and yearling body-conformation traits ranged from 0.02 to 0.28. Our GWAS highlighted a genomic window on chromosome 5 that was strongly associated with variation in AGEP4. We also identified 4 regions, located on chromosomes 14, 6, 1, and 11 (in order of decreasing importance), that exhibited suggestive associations with AGEP4. Our results show that AGEP4 is a reasonable predictor of estimated breeding values for fertility traits in lactating cows. Although the GWAS provided insights into genetic mechanisms underpinning AGEP4, further work is required to test genomic predictions of fertility that use this information.

Advancing research on teams and team effectiveness in implementation science: An application of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework.

Background: Effective teams are essential to high-quality healthcare. However, teams, team-level constructs, and team effectiveness strategies are poorly delineated in implementation science theories, models, and frameworks (TMFs), hindering our understanding of how teams may influence implementation. The Exploration, Preparation, Implementation, Sustainment (EPIS) framework is a flexible and accommodating framework that can facilitate the application of team effectiveness approaches in implementation science. Main Text: We define teams and provide an overview of key constructs in team effectiveness research. We describe ways to conceptualize different types of teams and team constructs relevant to implementation within the EPIS framework. Three case examples illustrate the application of EPIS to implementation studies involving teams. Within each study, we describe the structure of the team and how team constructs influenced implementation processes and outcomes. Conclusions: Integrating teams and team constructs into the EPIS framework demonstrates how TMFs can be applied to advance our understanding of teams and implementation. Implementation strategies that target team effectiveness may improve implementation outcomes in team-based settings. Incorporation of teams into implementation TMFs is necessary to facilitate application of team effectiveness research in implementation science.

Teams and team-level constructs are neglected in implementation theories, models, and frameworks (TMFs). This paper calls attention to the importance of teams in implementation research and practice and provides an overview of team effectiveness research for implementation science. We illustrate how the EPIS framework can be applied to advance our understanding of how teams influence implementation processes and outcomes. We identify future directions for research on teams and implementation, including developing and testing implementation strategies that focus on team effectiveness.

When the individual comes into play: The role of self and the partner in the dyadic play fighting of rats.

Social play in rats is rewarding and important for the development of brain and social skills. There are differences in the amount of play behavior displayed among individuals, with earlier studies suggesting that, despite variation across trials, individual differences tend to be consistent. In the present study, juvenile Lister-hooded rats were paired with a different, unfamiliar same-sex partner on three days and based on the amount of play each individual initiated, it was characterized as a high, medium or low player. Using this categorization, we explored three features related to individual differences. First, we show that by increasing the number of test days from two, as was done in a previous study (Lesscher et al., 2021), to three, characterization was effectively improved. Secondly, while the earlier study only used males, the present study showed that both sexes exhibit a similar pattern of individual differences in the degree of playfulness. Even though low players consistently initiated less play than medium and high players, all rats varied in how much play they initiated from one trial to the next. Thirdly, we assessed two potential mechanisms by which the playfulness of one rat can modify the level of playfulness of the other rat (i.e., emotional contagion vs homeostasis). Analyses of individuals' contribution to the play of dyads suggest that rats consistently adjust their play behavior depending on the behavior displayed by the partner. Since this adjustment can be positive or negative, our data support a homeostatic mechanism, whereby individuals increase or decrease the amount of play they initiate, which results in the experience of an overall stable pattern of play across trials. Future research will investigate the neural bases for individual differences in play and how rats maintain a preferred level of play.

Genome-wide association study of anogenital distance and its (co)variances with fertility in growing and lactating Holstein-Friesian dairy cattle.

Anogenital distance (AGD) is a moderately heritable trait that can be measured at a young age that may provide an opportunity to indirectly select for improved fertility in dairy cattle. In this study, we characterized AGD and its genetic and phenotypic relationships with a range of body stature and fertility traits. We measured AGD, shoulder height, body length, and body weight in a population of 5,010 Holstein-Friesian and Holstein-Friesian × Jersey crossbred heifers at approximately 11 mo of age (AGD1). These animals were born in 2018 across 54 seasonal calving, pasture-based dairy herds. A second measure of AGD was collected in a subset of herds (n = 17; 1,956 animals) when the animals averaged 29 mo of age (AGD2). Fertility measures included age at puberty (AGEP), then time of calving, breeding, and pregnancy during the first and second lactations. We constructed binary traits reflecting the animal's ability to calve during the first 42 d of their herd's seasonal calving period (CR42), be presented for breeding during the first 21 d of the seasonal breeding period (PB21) and become pregnant during the first 42 d of the seasonal breeding period (PR42). The posterior mean of sampled heritabilities for AGD1 was 0.23, with 90% of samples falling within a credibility interval (90% CRI) of 0.20 to 0.26, whereas the heritability of AGD2 was 0.29 (90% CRI 0.24 to 0.34). The relationship between AGD1 and AGD2 was highly positive, with a genetic correlation of 0.89 (90% CRI 0.82 to 0.94). Using a GWAS analysis of 2,460 genomic windows based on 50k genotype data, we detected a region on chromosome 20 that was highly associated with variation in AGD1, and a second region on chromosome 13 that was moderately associated with variation in AGD1. We did not detect any genomic regions associated with AGD2 which was measured in fewer animals. The genetic correlation between AGD1 and AGEP was 0.10 (90% CRI 0.00 to 0.19), whereas the genetic correlation between AGD2 and AGEP was 0.30 (90% CRI 0.15 to 0.44). The timing of calving, breeding, and pregnancy (CR42, PB21, and PR42) during first or second lactations exhibited moderate genetic relationships with AGD1 (0.19 to 0.52) and AGD2 (0.46 to 0.63). Genetic correlations between AGD and body stature traits were weak (≤0.16). We conclude that AGD is a moderately heritable trait, which may have value as an early-in-life genetic predictor for reproductive success during lactation.

Animal- and herd-level factors associated with onset of puberty in grazing dairy heifers.

AIMS: To explore animal- and herd-level risk factors influencing age at puberty in predominantly Holstein-Friesian dairy heifers managed in seasonal, pasture-based systems. METHODS: Heifers born in spring 2018 (n = 5,010) from 54 commercial dairy herds in New Zealand were visited on three occasions when the mean heifer age, within herd, was 10 (visit 1; V1), 11 (V2) and 12 (V3) months old. Blood samples were collected on each visit and liveweight, stature and anogenital distance (AGD) were measured at V2. Heifers were defined as having reached puberty at the first visit where blood progesterone was elevated (≥ 1 ng/mL). Animal-level response variables included pubertal status by V1, V2 and V3, and age at puberty (or age at V3 plus 31 days for those that had not attained puberty by V3). To explore herd-level management factors, farmers answered a questionnaire relating to animal location, land type, health, feeding, and management between weaning and mating. A partial least squares regression was undertaken to identify herd-level factors associated with the greatest influence on puberty rate within herd. RESULTS: The mean age at puberty was 352 (SD 34.9) days. Heavier animals at a greater proportion of expected mature liveweight based on their breeding value for liveweight, or animals with a higher breed proportion of Jersey and lower breed proportion of Holstein, were associated with earlier puberty. Herd puberty rates varied widely among enrolled herds, and averaged 20%, 39% and 56% by V1, V2 and V3, respectively. Liveweight, followed by breed and land type, had the greatest influence on the herd puberty rate. Heifer herds with a greater mean liveweight (absolute and proportion of expected mature weight) or greater Jersey proportion had more animals that reached puberty at any visit, whereas herds located on steep land or with greater Holstein breed proportions had lower puberty rates. Management-related factors such as vaccinations, provision of feed supplements, and weighing frequency were also herd-level risk factors of puberty but had less influence. CONCLUSIONS AND CLINICAL RELEVANCE: This study highlights the importance of having well-grown heifers for increasing the chances of earlier puberty onset and the effect of breed and youngstock management to achieve growth targets. These outcomes have important implications for the optimal management of heifers to achieve puberty before their maiden breeding and for the timing of measurements to potentially incorporate a puberty trait in genetic evaluations.

Effect of nonsteroidal anti-inflammatory drugs on the inflammatory response of bovine endometrial epithelial cells in vitro.

Chronic postpartum uterine infection detrimentally affects subsequent fertility. Nonsteroidal anti-inflammatory drugs (NSAID) are used to alleviate pain and treat inflammatory conditions in transition dairy cows with varying success. To screen the efficacy of NSAID in the absence of animal experiments, we have established an in vitro model to study uterine inflammation. Inflammation was induced in cultured bovine endometrial epithelial cells by challenging cells with an inflammation cocktail: lipopolysaccharide and proinflammatory cytokines, interleukin-1ß (IL1ß) and tumor necrosis factor α (TNFα). Release of the inflammation markers, serum amyloid A (SAA) and α-1-acid glycoprotein (αAGP), was measured by ELISA. Concentration of these markers was used to indicate the effectiveness in dampening inflammation of 5 NSAID: meloxicam, flunixin meglumine, aspirin, ketoprofen, and tolfenamic acid. Three NSAID, meloxicam, flunixin meglumine, and tolfenamic acid, were successful at dampening the release of SAA and αAGP into cell-culture supernatant, and the corresponding treated cells were selected for down-stream mRNA expression analysis. Expression of 192 genes involved in regulation of inflammatory pathways were investigated using Nanostring. Of the genes investigated, 81 were above the mRNA expression-analysis threshold criteria and were included in expression analysis. All SAA genes investigated (SAA2, SAA3, M-SAA3.2) were upregulated in response to the inflammation cocktail, relative to mRNA expression in control cells; however, AGP mRNA expression was below the expression analysis threshold and was, therefore, excluded from analysis. Treatment with NSAID downregulated genes involved in regulating chemokine signaling (e.g., CXCL2, CXCR4, CXCL5, and CXCL16) and genes that regulate the eicosanoid pathway (e.g., LTA4H, PTGS2, PLA2G4A, and PTGDS). Of the 5 NSAID investigated, meloxicam, flunixin meglumine, and tolfenamic acid are recommended for further investigation into treatment of postpartum uterine inflammation. The results from this study confirm the immunomodulatory properties of the endometrial epithelium in response to inflammatory stimuli and suggest that NSAID may be beneficial in alleviating uterine inflammation.

A Lexical Approach to Assessing Stress: Development and Proof-of-Concept.

OBJECTIVE: We describe a methodology that provides a nonobtrusive means of detecting stress and related deficits through the assessment of spontaneous verbal output in ongoing communications. BACKGROUND: In high-demand environments, operational personnel are exposed to an array of environmental, task, and interpersonal stressors that can negatively impact performance as well as jeopardize safety and well-being. In these settings, the requirement exists to assess cognitive and emotional state "at a distance" and without interfering with ongoing performance. METHOD: We describe a lexical approach to assessing stress effects from ongoing or spontaneous verbal output. This approach is examined in a spaceflight analog setting. RESULTS: We assess stress effects in terms of five core dimensions and develop lexical indicators of these core stress dimensions and relevant sub-facets. We establish the proof-of-concept of this approach by presenting representative data from a spaceflight analog. CONCLUSION: This approach provides an unobtrusive means to evaluate ongoing task communications at the individual and team level in order to assess cognitive/emotional states such as workload, negative affect, attentional focus, anxiety, and team orientation. APPLICATION: There are many high-demand settings in which it is valuable to monitor the potential negative effects of stress on operational personnel. These environments include spaceflight, the military, aviation, law enforcement, and medicine.

Variance parameter estimation for age at puberty phenotypes under 2 levels of phenotype censorship.

Age at puberty (AGEP) is a moderately heritable trait in cattle that may be predictive of an animal's genetic merit for reproductive success later in life. In addition, under some mating strategies (for example, where mating begins before all animals have attained puberty) animals that attain puberty at a relatively young age will also likely conceive earlier than their herd mates, and thus begin their productive life earlier. Unfortunately, AGEP is challenging to measure because animals must be observed over a period of several months. Our objectives for this study were twofold. The first objective was to produce variance components for AGEP. The second objective was to investigate the implications of a simplified phenotyping strategy for AGEP, when the interval between repeated blood plasma progesterone measures was extended from weekly to monthly, increasing the extent of left, interval, and right censoring. We measured AGEP in a closely monitored population of around 500 Holstein-Friesian heifers, born in 2015 and managed under a seasonal, pasture-based dairy system. Animals were blood tested weekly from approximately 240 to 440 d of age and were deemed to have reached puberty when blood plasma progesterone elevation (>1 ng/mL) was detected in 2 of 3 consecutive blood tests (AGEP_Weekly). To simulate a simplified phenotyping strategy based on monthly herd visits (AGEP_Monthly), we selectively disregarded data from all but 3 blood test events, when animals were around 300, 330, and 360 d of age (standard deviation = 14.5 d). The posterior mean of estimated heritabilities for AGEP_Weekly was 0.54, with a 90% credibility interval (90% CRI) of 0.41 to 0.66, whereas it was 0.44 (90% CRI 0.32 to 0.57) for AGEP_Monthly. The correlation between EBVs for AGEP_Weekly and AGEP_Monthly was 0.87 (90% CRI, 0.84 to 0.89). We conclude that in this population, AGEP is a moderately heritable trait. Further, increasing phenotype censorship from weekly to monthly observations would not have altered the main conclusions of this analysis. Our results support the strategic use of censoring to reduce costs and animal ethics considerations associated with collection of puberty phenotypes.

The first week following insemination is the period of major pregnancy failure in pasture-grazed dairy cows.

A 60% pregnancy success for inseminations is targeted to optimize production efficiency for dairy cows within a seasonal, pasture-grazed system. Routine measures of pregnancy success are widely available but are limited, in practice, to a gestation stage beyond the first 28 d. Although some historical data exist on embryonic mortality before this stage, productivity of dairy systems and genetics of the cows have advanced significantly in recent decades. Accordingly, the aim was to construct an updated estimate of pregnancy success at key developmental stages during the first 70 d after insemination. Blood samples were collected for progesterone concentrations on d 0 and 7. A temporal series of 4 groups spanning fertilization through d 70 were conducted on 4 seasonal, pasture-grazed dairy farms (n = 1,467 cows) during the first 21 d of the seasonal breeding period. Morphological examination was undertaken on embryos collected on d 7 (group E7) and 15 (group E15), and pregnancy was diagnosed via ultrasonography on approximately d 28 and 35 (group E35) as well as d 70 (group E70). Fertilization, embryo, and fetal evaluation for viability established a pregnancy success pattern. Additionally, cow and on-farm risk factor variables associated with pregnancy success were evaluated. We estimated pregnancy success rates of 70.9%, 59.1%, 63.8%, 62.3%, and 56.7% at d 7, 15, 28, 35, and 70, respectively. Fertilization failure (15.8%) and embryonic arrest before the morula stage (10.3%) were the major developmental events contributing to first-week pregnancy failures. Embryo elongation failure of 7% contributed to pregnancy failure during the second week. The risk factors for pregnancy success that were related to the cows included interval between calving and insemination, and d-7 plasma progesterone concentrations, whereas insemination sire was associated with pregnancy outcome. Most pregnancy failure occurs during the first week among seasonal-calving pasture-grazed dairy cows.

Who's laughing? Play, tickling and ultrasonic vocalizations in rats.

Social play in rats is a highly rewarding, energetic form of social interaction and important for development of the brain and social skills. The 50 kHz ultrasonic vocalizations (USV) emitted during social play are thought to be an expression of a positive affective state (laughter), which in some situations may also function as communication signals. Heterospecific play, 'tickling' by an experimenter, is thought to simulate conspecific play, and has been used to improve welfare and to study the neurobiology of positive affect. Given that tickling evokes substantial amounts of USV, we investigated whether heterospecific play is simulating conspecific play by comparing USV-behaviour associations in both contexts. If the 50 kHz calls are merely an expression of 'laughter' then the pattern and type of emission in both contexts should be similar. By contrast, as playing with a conspecific involves a two-way exchange of signalling, the additional demands on communication should lead to a different pattern of calling. While calling was prevalent in both types of play, how the different types of 50 kHz calls are used in the two contexts differed markedly. The findings suggest that while conspecific and heterospecific play are positive experiences, tickling is not the equivalent of conspecific play. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.

Prevention and early treatment of the long-term physical effects of COVID-19 in adults: design of a randomised controlled trial of resistance exercise-CISCO-21.

BACKGROUND: Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection. METHODS: A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID. Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea. DISCUSSION: Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals. TRIAL REGISTRATION: ClinicialTrials.gov NCT04900961 . Prospectively registered on 25 May 2021.

Adaptive immune response ranking is associated with reproductive phenotypes in grazing dairy cows divergent in genetic merit for fertility traits.

A strong adaptive immune response has been reported to have positive effects on fertility; therefore, we investigated antibody- and cell-mediated adaptive immune responses (AMIR and CMIR, respectively) and their associations with reproductive phenotypes using a population of animals that differed in their estimated genetic merit for fertility traits (fertility breeding value; FertBV). Holstein-Friesian heifers (n = 528) grazed on pasture in 4 herds based on age. These herds included 277 heifers of positive (POS) FertBV and 251 of negative (NEG) FertBV. The adaptive immune response (IR) was evaluated before puberty at 7.5 mo of age and used to rank animals as high, average, or low for AMIR, CMIR, and overall IR (combined CMIR and AMIR). The animals were studied from 12 wk of age through to the end of their second lactation to measure growth, puberty, and timing and success of fertility phenotypes, including those related to ovulation and pregnancy. Initial analysis indicated no difference in fertility outcomes between cows ranked as high or average for AMIR (n = 55, n = 407, respectively), CMIR (n = 87, n = 354, respectively), and IR (n = 29, n = 470, respectively), so these groups were pooled as HiAv-IR. Proportions of heifers of POS FertBV were similar within HiAv and low categories across AMIR (0.52 and 0.58, respectively), CMIR (0.51 and 0.59, respectively), and IR (0.53 and 0.48, respectively). Heifers with HiAv-IR had a greater average daily weight gain from 13 to 52 wk of age (661 g, 95% confidence interval 652, 669 vs. 619 g, 95% confidence interval 591, 647) and tended to be younger at puberty (371 d, 95% confidence interval 366, 377 vs. 385 d, 95% confidence interval 369, 401) than low-IR heifers. Low-CMIR cows of a NEG FertBV had a >40 d longer calving to first ovulation interval during their first lactation compared with HiAv-CMIR NEG FertBV cows. Low-CMIR cows also had decreased pregnancy rates at both 3 wk (25% ± 7% vs. 42% ± 3%; least squares means ± standard error) and 6 wk (33% ± 7% vs. 54% ± 3%; least squares means ± standard error) into the seasonal breeding period during their first lactation, compared with HiAv-CMIR cows. In summary, although the number of POS and NEG FertBV cows was similar in each immune group; interaction effects between FertBV and immune ranking on reproductive phenotypes are evident when cows were ranked by the overall IR. There were also associations between dairy cows' CMIR ranking and ability to return to estrus and become pregnant early in the breeding period, which will have benefits in seasonal breeding systems.

Relationships between prostaglandin concentrations, a single nucleotide polymorphism in HSD17B12, and reproductive performance in dairy cows.

Prostaglandins are involved in multiple processes important for fertility, with previous work in mice highlighting a potential role for the HSD17B12 gene in prostaglandin biosynthesis. This study aimed to determine the associations among circulating prostaglandin concentrations, a missense SNP in the HSD17B12 gene predicted to disrupt protein function, and fertility traits in first-lactation Holstein-Friesian dairy cows. We used a study population of approximately 500 animals specifically bred to have either a positive (POS, +5%) or negative (NEG, -5%) genetic merit for fertility (FertBV). Genotypes of a previously identified SNP (rs109711583) in HSD17B12 were determined, with 116 animals genotyped as AA, 215 genotyped as AG, and 153 genotyped as GG. Plasma concentrations of prostaglandin E2 and the PGF2α metabolite PGFM were determined at 3 time points (12 mo of age, 4 d postpartum, and 5 wk postpartum during first lactation) in a selection of animals with AA and GG genotypes from both the POS and NEG FertBV groups (n = 33-40 in each genotype for each FertBV group). Binary reproductive traits (yes or no) examined included submission for artificial breeding in the first 3 or 6 wk of the seasonal breeding period; conception to first service; conception during the first 6 wk of the breeding period; and pregnant at the end of the breeding period. Uterine health at 6 wk after calving was examined by evaluating the percentage of polymorphonuclear leukocytes following uterine cytology and by scoring vaginal discharge based on the presence of purulent material. The 3-wk submission rate was increased in animals that carried the G allele of the missense SNP in HSD17B12, but no differences were present among genotypes for 6-wk submission rate. The trait was additive, with each increase of the G allele increasing the 3-wk submission rate by 6 to 7%. We did not observe any consistent associations between SNP alleles and circulating PGE2 concentrations; however, a complex 3-way interaction among time, fertility group, and SNP allele was present for PGFM concentrations. Plasma concentrations of PGE2 were increased approximately 40% at 5 wk postpartum in animals that were submitted for breeding within 3 or 6 wk of the start of the breeding season, and in those that conceived during the first 6 wk of breeding, compared with those that did not. Plasma concentrations of PGFM were decreased approximately 20% in those animals that conceived to their first service and tended to be decreased in animals that were pregnant at the end of the breeding period, compared with those that were not. In summary, associations were observed between the SNP in HSD17B12 and submission rate by d 21 of the breeding season, as well as between circulating prostaglandin concentrations and fertility traits, but the SNP was not consistently linked to changes in prostaglandin concentrations. Thus, the association between submission rate by d 21 of the breeding season and the SNP in HSD17B12 were unlikely driven by changes in prostaglandins.

Response to kisspeptin and gonadotropin-releasing hormone agonist administration in Holstein-Friesian dairy heifers with positive or negative genetic merit for fertility traits.

Previous research has identified that Holstein-Friesian dairy heifers with positive (POS) genetic merit for fertility traits (FertBV) reach puberty earlier than heifers with negative (NEG) FertBV. The hypothalamus-pituitary-gonadal (HPG) axis is functional in heifers before the onset of puberty, with increased LH release evident as heifers progress toward puberty. We investigated the functionality of the HPG axis in peripubertal Holstein-Friesian dairy heifers with divergent POS or NEG FertBV, hypothesizing that the earlier puberty onset of POS heifers is associated with earlier activation of the HPG axis than in NEG heifers. In experiment 1, we tested the dose responsiveness of POS heifers to an intravenous injection of either kisspeptin [Kiss; 2, 4, or 8 µg/kg of body weight (BW); n = 3 per dose] or a GnRH agonist (buserelin; 5, 10, or 20 ng/kg of BW; n = 3 per dose). The use of these 2 agonists investigates the status of the HPG axis in both the hypothalamus (Kiss) and pituitary (buserelin) glands. Doses of 4 µg/kg BW of Kiss and 10 ng/kg BW of buserelin produced submaximal LH responses and were used in experiment 2, in which previously unused POS (n = 22) and NEG (n = 18) FertBV heifers were challenged with both agonists at 10 and 12 mo of age in a partial crossover design. Heifers were randomly allocated to treatment groups, balanced for age and BW. The LH response to buserelin was greater in POS heifers than NEG heifers at 10 mo of age, with no difference in response at 12 mo. The FSH response to buserelin and the LH and FSH responses to Kiss did not differ between the POS and NEG heifers at either age. These results indicate an association between divergent genetic merit for fertility and the LH release to buserelin at 10 mo of age, supporting the hypothesis that gonadotropin responsiveness to a GnRH agonist is more advanced in POS heifers than in NEG heifers.

Temporal profiles describing markers of inflammation and metabolism during the transition period of pasture-based, seasonal-calving dairy cows.

The physiology of the dairy cow while transitioning from pregnancy to lactation is complex, with multifactorial processes studied extensively for the role they play in manifestation of disease along with associated economic losses and compromised animal welfare. Manuscripts outlining associations among nutrition, production, physiology, and genetics variables and transition cow disorders are common in literature, with blood analytes that are central to energy metabolism (e.g., nonesterified fatty acids; NEFA, ß-hydroxybutyrate; BHB) often reported. Immunity and inflammation have increasingly been explored in the pathogenesis and persistence of disorders, with cytokines and acute phase proteins well documented. However, most of these studies have involved cows fed total mixed rations, which may not always reflect profiles of blood analytes and other physiological indicators of transition cow health in grazing cows consuming fresh pasture. Considering the comparatively lesser characterization of these analytes and markers in pasture-based, seasonal-calving dairy cows, we compiled a database consisting of 2,610 cow lactations that span 20 yr of transition cow research in New Zealand. Using this database, analyte profiles from approximately 28 d precalving to 35 d postcalving were identified in dairy cows with a range of genetics, milk production potentials, and pasture-based farm management systems. These profiles characterize changes in energy reserves and metabolism (NEFA, BHB, glucose, insulin, growth hormone, insulin-like growth factor-1, leptin, body condition score, body weight), liver function (globulin, aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, cholesterol, liver triacylglycerides), protein metabolism (albumin, total protein, albumin:globulin ratio, creatinine, urea, creatine kinase), mineral balance (calcium, magnesium, phosphate, potassium, sodium, chloride, bicarbonate), inflammation (IL-1ß, IL-6, haptoglobin, reactive oxygen species, total antioxidant capacity), and uterine health (polymorphonuclear cells, macrophage cells, vaginal discharge score). Temporal changes are generally consistent with previously characterized homeorhetic changes experienced by the dairy cow during the transition from pregnancy to lactation in both pastoral and housed systems. Some of the profiles had not previously been presented for pastoral systems, or in some cases, presented for either system. Our results indicate that moderate-yielding dairy cows undergo similar homeorhetic changes to high-yielding housed cows; however, differences in diet composition result in greater BHB concentrations than expected, based on their milk production and NEFA concentrations. In addition, most cows were able to transition to a state of higher energy requirement following calving, albeit with an increased metabolic challenge in the liver, and only a small percentage of cows were classified with severe hepatic lipidosis or severe hyperketonemia. Increases in metabolic function of the liver were accompanied by changes in indicators of the immune system and changes in mineral balance that, combined, probably reflect the innate response to the transition from gestation to lactation.

Measuring Play Fighting in Rats: A Multilayered Approach.

Rough-and-tumble play or play fighting is an important experience in the juvenile period of many species of mammals, as it facilitates the development of social skills, and for some species, play fighting is retained into adulthood as a tool for assessing and managing social relationships. Laboratory rats have been a model species for studying the neurobiology of play fighting and its key developmental and social functions. However, play fighting interactions are complex, involving competition and cooperation; therefore, no single measure to quantify this behavior is able to capture all its facets. Therefore, in this paper, we present a multilayered framework for scoring all the relevant facets of play that can be affected by experimental manipulations and the logic of how to match what is measured with the question being asked. © 2022 Wiley Periodicals LLC.

Development of an intrauterine infection model in the postpartum dairy cow.

AIMS: To develop an intrauterine infection model for Trueperella pyogenes in postpartum dairy cows and to assess the effect of this infection on the degree of intrauterine inflammation and concentrations of progesterone in serum. METHODS: The oestrous cycles of 36 healthy, non-pregnant, postpartum dairy cows were synchronised. They were then treated by intrauterine infusion of 0.5 g cephapirin before being blocked by age and randomly assigned to treatment with intrauterine infusion of saline (n = 18), 107 (n = 9) or 109 (n = 9) cfu of T. pyogenes, approximately 4 days after the expected time of ovulation (Day 0). Prior to intrauterine infusion on Day 0 and again on Days 3, 7, 10, and 15, cytobrush samples were collected from the uterus of each cow for microbiology and assessment of the percentage of polymorphonuclear neutrophils (PMN%). Blood samples were collected on the same days for measurement of concentrations of progesterone in serum, and uterine lumen diameter was assessed daily using transrectal ultrasonography. RESULTS: Trueperella pyogenes was isolated from 5/18 (28%), 7/9 (78%) and 8/9 (89%) cows infused with saline, 107 or 109 cfu of T. pyogenes, respectively (p < 0.001). Mean PMN% in the control cows did not change over time (p > 0.05), whereas it was higher on Days 7 and 10 than Day 0 in the 107 cfu group, and higher on Days 3 and 10 than Day 0 in the 109 cfu group (p < 0.05). The percentage of observations with uterine lumen diameters >2 mm was higher in cows infused with 107 (29.3 (95% CI = 14.5-44.2)%) or 109 cfu (19.2 (95% CI = 7.0-31.5)%) than in control cows (3.1 (95% CI = 0.1-6.0)%) (p < 0.001). Mean concentrations of progesterone in serum were higher in cows infused with 107 cfu (2.01 (SE 0.19) ng/mL) than cows infused with 109 cfu (1.01 (SE 0.27) ng/mL), with the control group intermediate (1.41 (SE 0.19) ng/mL) (p = 0.03). CONCLUSIONS: Infusion of 107 or 109 cfu of T. pyogenes resulted in the establishment of intrauterine infection in 83% of cows. Infection resulted in increased uterine lumen diameter, and an inflammatory response, i.e. elevated PMN%. CLINICAL RELEVANCE: This intrauterine infection model may be useful for future research on, for example, the pathogenesis of intrauterine infection in postpartum dairy cows.