Robustness and sustainable breeding: pathophysiological and molecular hypotheses

The hypothalamic-pituitary adrenocortical (HPA) axis is the most important stress-responsive neuroendocrine system. Cortisol (or corticosterone) released by the adrenal cortices exerts a large range of effects on themetabolisms, the immune system, inflammatory processes, and brain function, for example. Large individual variations have been described in HPA axis activity, with important physiopathological consequences. In terms of animal production, higher cortisol levels have negative effects on growth rate and feed efficiency and increases the fat/lean ratio of carcasses. On the contrary, cortisol has positive effects on traits related to robustness and adaptation, such as newborn survival or tolerance to heat stress. Intense selection for lean tissue during the last decades has reduced concomitantly the activity of the corticotropic axis,with negative consequences of selection on piglet survival for instance.One strategy to improve robustness is to select animalswith higher HPA axis activity. Research on themolecularmechanisms of this variability is very active. The objective is to identifymarkers that could be used to select animalswith higher HPA axis activity, and thus improve their robustnesswithout damaging their production potential,which is the primary selection objective in the development of “sustainable” farming.L'axe corticotrope est le système neuroendocrinien le plus important dans les réponses de stress. Le cortisol (ou la corticostérone) libéré par le cortex des glandes surrénales exerce de nombreux effets sur les métabolismes, le système immunitaire et les processus inflammatoires, ainsi que sur les fonctions cérébrales. Il existe une large variabilité interindividuelle dans le fonctionnement de cet axe, avec des conséquences fonctionnelles importantes. En termes de production animale, des niveaux élevés de cortisol ont des effets négatifs sur la vitesse de croissance, l'efficacité alimentaire ou la composition de carcasse. Au contraire, le cortisol a des effets positifs sur les caractères de robustesse et d'adaptation comme la survie des nouveaux-nés ou la résistance à la chaleur. Au cours des dernières décennies, une intense sélection sur la production de tissu maigre chez le Porc a réduit concomitamment l'activité de l'axe corticotrope, avec des conséquences négatives sur la survie des nouveau-nés par exemple. Une importante variabilité génétique est présente dans toutes les composantes de l'axe corticotrope. La recherche des mécanismes moléculaires de cette variabilité est très active et devrait ouvrir la voie à une sélection sur marqueurs, en vue d'optimiser le fonctionnement de l'axe corticotrope pour maximiser les effets favorables sur la robustesse des animaux, tout en préservant leur potentiel de production, objectif de sélection prioritaire dans le cadre du développement d'un élevage « durable »

Pig welfare : the animal point of view, biological and behavioural approaches

Welfare refers to the subjective psychological state of an individual regarding his internal and external environment. Since we are not yet able to read directly animal emotions and feelings, we have no other option than to infer them from the analysis of objective signs, particularly physiological and behavioural, based on the psychobiology of emotion, stress and adaptation. The activation of neuroendocrine stress systems (adrenocortical axis and sympathetic nervous system) provides numerous markers to study biological responses to environmental factors. However, their interpretation in terms of welfare must take into account the important role of these systems in the body’s general physiology. Behavioural criteria are also used (analysis of time budget and space use, abnormal behaviours, expression of social links, preference tests), and interpreted in the context of applied ethology.Le bien-être fait référence à l'état psychologique subjectif de l'individu par rapport à son environnement interne et externe. Puisque nous ne sommes pas encore capables de lire directement les sensations et les émotions de l'animal, nous en sommes réduits à les inférer de l'analyse de leurs manifestations objectives, en particulier physiologiques et comportementales, qui ont été étudiées dans le contexte de la psychobiologie des émotions, du stress et de l'adaptation. L'activation des systèmes neuroendocriniens de réponse au stress (axe corticotrope et système nerveux sympathique) fournissent de nombreux marqueurs pour l'étude des réponses biologiques aux facteurs d'environnement. Cependant leur interprétation en termes de bien-être devra prendre en considération le rôle de ces systèmes dans la physiologie générale de l'organisme. On utilisera aussi des critères comportementaux (analyse du budget-temps et de l'utilisation de l'espace, comportements anormaux, expression des liens sociaux, tests de préférences) qu'il faudra analyser dans le contexte des acquis de l'éthologie appliquée

Le mal-être active les gènes codant pour l'inflammation

Les chevaux agressifs ne sont pas simplement des chevaux mal éduqués ou caractériels. Cette agressivité peut révéler des souffrances physiques et un état de mal-être qui peuvent être profonds. Cet état de mal-être va jusqu’à modifier l’expression de certains de leurs gènes : ceux impliqués dans la réponse immunitaire et au stress, et la mort cellulaire programmée. Cela montre à quel point ce trouble ne doit pas être pris à la légère. Les chevaux qui présentent un trouble agressif doivent être pris en charge afin de faire évoluer leurs conditions de vie et de travail vers une meilleure prise en compte de leur bien-être

Seasonal effects on plasma cortisol concentrations in the Bedouin buck: circadian studies and response to ACTH

Our work aims at the exploration of cortisol secretion in the Bedouin goat, native to the Algerian Sahara desert, to understand the mechanisms of adaptation to extreme hot climates. In the present study, diurnal and seasonal variations of cortisol concentrations were measured in basal conditions, as well as the response to ACTH stimulation tests across seasons in bucks. The plasma concentrations of cortisol showed no diurnal cycle but a large variation across seasons. The highest levels occurred in summer and winter when the environmental conditions are at their extreme levels. The rectal temperature showed nychthemeral and seasonal variations, and BW was also different across seasons with highest values in summer and lowest in winter. The results obtained after administration of two doses (2 or 10 ?g/kg BW) of synthetic ACTH to three different age groups (kids, adults and elderly animals) showed a strong increase in plasma cortisol concentrations under all conditions with maximum levels achieved between 15 and 120 min. The analysis of the area under the cortisol curve showed no significant difference between the responses to the two doses of ACTH and between age groups, but showed seasonal variations with the lowest response in autumn than in other seasons. We conclude that season significantly affects secretion of cortisol in both basal state and under ACTH stimulation. However, the variation of adrenal reactivity to ACTH is not sufficient to explain seasonal differences, and in particular the summer peak in basal circulating cortisol concentrations. Further research should focus on the respective contribution of environmental factors (such as day length, temperature, humidity) and the mechanisms involved in cortisol regulation

Association of HPA axis-related genetic variation with stress reactivity and aggressive behaviour in pigs

<p>Abstract</p> <p>Background</p> <p>Stress, elicited for example by aggressive interactions, has negative effects on various biological functions including immune defence, reproduction, growth, and, in livestock, on product quality. Stress response and aggressiveness are mutually interrelated and show large interindividual variation, partly attributable to genetic factors. In the pig little is known about the molecular-genetic background of the variation in stress responsiveness and aggressiveness. To identify candidate genes we analyzed association of DNA markers in each of ten genes (<it>CRH </it>g.233C>T, <it>CRHR1 </it>c.*866_867insA, <it>CRHBP </it>c.51G>A, <it>POMC </it>c.293_298del, <it>MC2R </it>c.306T>G, <it>NR3C1 </it>c.*2122A>G, <it>AVP </it>c.207A>G, <it>AVPR1B </it>c.1084A>G, <it>UCN </it>g.1329T>C, <it>CRHR2 </it>c.*13T>C) related to the hypothalamic-pituitary-adrenocortical (HPA) axis, one of the main stress-response systems, with various stress- and aggression-related parameters at slaughter. These parameters were: physiological measures of the stress response (plasma concentrations of cortisol, creatine kinase, glucose, and lactate), adrenal weight (which is a parameter reflecting activity of the central branch of the HPA axis over time) and aggressive behaviour (measured by means of lesion scoring) in the context of psychosocial stress of mixing individuals with different aggressive temperament.</p> <p>Results</p> <p>The SNP <it>NR3C1 </it>c.*2122A>G showed association with cortisol concentration (p = 0.024), adrenal weight (p = 0.003) and aggressive behaviour (front lesion score, p = 0.012; total lesion score p = 0.045). The SNP <it>AVPR1B </it>c.1084A>G showed a highly significant association with aggressive behaviour (middle lesion score, p = 0.007; total lesion score p = 0.003). The SNP <it>UCN </it>g.1329T>C showed association with adrenal weight (p = 0.019) and aggressive behaviour (front lesion score, p = 0.029). The SNP <it>CRH </it>g.233C>T showed a significant association with glucose concentration (p = 0.002), and the polymorphisms <it>POMC </it>c.293_298del and <it>MC2R </it>c.306T>G with adrenal weight (p = 0.027 and p < 0.0001 respectively).</p> <p>Conclusions</p> <p>The multiple and consistent associations shown by SNP in <it>NR3C1 </it>and <it>AVPR1B </it>provide convincing evidence for genuine effects of their DNA sequence variation on stress responsiveness and aggressive behaviour. Identification of the causal functional molecular polymorphisms would not only provide markers useful for pig breeding but also insight into the molecular bases of the stress response and aggressive behaviour in general.</p

Spontaneous intake of essential oils after a negative postnatal experience has long-term effects on blood transcriptome in chickens

Chicks subjected to early stressful factors could develop long-lasting effects on their performances, welfare and health. Free access to essential oils (EO) in poultry farming could mitigate these effects and potentially reduce use of antimicrobial drugs. This study on chicken analyzed long-lasting effects of post-hatch adverse conditions (Delayed group), and the impact of EO intake on blood physiological parameters and transcriptome. Half of the Control and Delayed groups had free access to EO, while the other half had only water for the first 13 days post-hatching. Blood analyses of metabolites, inflammation and oxidative stress biomarkers, and mRNA expression showed sex differences. Long-lasting effects of postnatal experience and EO intake persisted in blood transcriptome at D34. The early adverse conditions modified 68 genes in males and 83 genes in females. In Delayed males six transcription factors were over-represented (NFE2L2, MEF2A, FOXI1, Foxd3, Sox2 and TEAD1). In females only one factor was over-represented (PLAG1) and four under-represented (NFIL3, Foxd3, ESR2 and TAL

Priming for welfare: gut microbiota is associated with equitation conditions and behavior in horse athletes

We simultaneously measured the fecal microbiota and multiple environmental and host-related variables in a cohort of 185 healthy horses reared in similar conditions during a period of eight months. The pattern of rare bacteria varied from host to host and was largely different between two time points. Among a suite of variables examined, equitation factors were highly associated with the gut microbiota variability, evoking a relationship between gut microbiota and high levels of physical and mental stressors. Behavioral indicators that pointed toward a compromised welfare state (e.g. stereotypies, hypervigilance and aggressiveness) were also associated with the gut microbiota, reinforcing the notion for the existence of the microbiota-gut-brain axis. These observations were consistent with the microbiability of behaviour traits (> 15%), illustrating the importance of gut microbial composition to animal behaviour. As more elite athletes suffer from stress, targeting the microbiota offers a new opportunity to investigate the bidirectional interactions within the brain gut microbiota axis.info:eu-repo/semantics/publishedVersio

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1–24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, rp=0.539; genetic correlation, rg=0.938). Post-ACTH cortisol levels were highly heritable (h2=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic–pituitary–adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but also point at pigs as a relevant model to explore the underlying mechanisms of the metabolic syndrome including the contribution of genetic factors

Gut microbiota resilience in horse athletes following holidays out to pasture

Elite horse athletes that live in individual boxes and train and compete for hours experience longterm physical and mental stress that compromises animal welfare and alters the gut microbiota. We therefore assessed if a temporary period out to pasture with conspecifics could improve animal welfare and in turn, favorably affect intestinal microbiota composition. A total of 27 athletes were monitored before and after a period of 1.5 months out to pasture, and their fecal microbiota and behavior profiles were compared to those of 18 horses kept in individual boxes. The overall diversity and microbiota composition of pasture and control individuals were temporally similar, suggesting resilience to environmental challenges. However, pasture exposure induced an increase in Ruminococcus and Coprococcus that lasted 1-month after the return to individual boxes, which may have promoted beneficial effects on health and welfare. Associations between the gut microbiota composition and behavior indicating poor welfare were established. Furthermore, withdrawn behavior was associated with the relative abundances of Lachnospiraceae AC2044 group and Clostridiales family XIII. Both accommodate a large part of butyrate-producing bacterial genera. While we cannot infer causality within this study, arguably, these findings suggest that management practices maintained over a longer period of time may moderate the behavior link to the gut ecosystem beyond its resilience potential

Transcriptomic signaling pathways involved in a naturalistic model of inflammation-related depression and its remission

This study aimed at identifying molecular biomarkers of inflammation-related depression in order to improve diagnosis and treatment. For this, we performed whole-genome expression profiling from peripheral blood in a naturalistic model of inflammation-associated major depressive disorder (MDD) represented by comorbid depression in obese patients. We took advantage of the marked reduction of depressive symptoms and inflammation following bariatric surgery to test the robustness of the identified biomarkers. Depression was assessed during a clinical interview using Mini-International Neuropsychiatric Interview and the 10-item, clinician-administered, Montgomery-Asberg Depression Rating Scale. From a cohort of 100 massively obese patients, we selected 33 of them for transcriptomic analysis. Twenty-four of them were again analyzed 4-12 months after bariatric surgery. We conducted differential gene expression analyses before and after surgery in unmedicated MDD and non-depressed obese subjects. We found that TP53 (Tumor Protein 53), GR (Glucocorticoid Receptor), and NF kappa B (Nuclear Factor kappa B) pathways were the most discriminating pathways associated with inflammation-related MDD. These signaling pathways were processed in composite z-scores of gene expression that were used as biomarkers in regression analyses. Results showed that these transcriptomic biomarkers highly predicted depressive symptom intensity at baseline and their remission after bariatric surgery. While inflammation was present in all patients, GR signaling over-activation was found only in depressed ones where it may further increase inflammatory and apoptosis pathways. In conclusion, using an original model of inflammation-related depression and its remission without antidepressants, we provide molecular predictors of inflammation-related MDD and new insights in the molecular pathways involved