Genetic variability of hpa axis function in pigs : Molecular mechanisms and consequences on meat production

Cortisol, released by the adrenal cortex in response to the pituitary hormone ACTH, is a typical glucocorticoid hormone, i.e. it induces peripheral catabolism, particularly of tissue proteins and stimulates the synthesis of glycogen (neoglucogenesis) in the liver. Therefore, high HPA (hypothalamic-pituitary- adrenocortical) axis activity increases fat deposition at the expense of tissue proteins. The HPA axis activity is subject to a wide genetic variability affecting its different levels of organisation, the amount of cortisol secreted (mainly dependent upon the adrenal cortex sensitivity to ACTH), its bioavailability (transport and metabolic processes), and its tissue action based on the efficacy of the receptors and their signalling pathways. This paper illustrates the genetic variability of cortisol production in pigs and its relationships with adiposity and meat quality. In a second part, we describe the different approaches used to identify the genes whose polymorphisms explains this genetic variability. These polymorphisms may be used to select animals with an optimal corticotrophic phenotype based on production objectives.Le cortisol libéré par le cortex des glandes surrénales sous contrôle de l'ACTH a une activité glucocorticoïde qui se traduit par un catabolisme périphérique, en particulier, des protéines tissulaires et une néosynthèse hépatique de protéines et de glucides (néoglucogenèse). Une forte activité corticotrope se traduit globalement par une augmentation de l'adiposité au détriment des protéines. Il existe une grande variabilité génétique dans le fonctionnement de l'axe corticotrope à différents niveaux, quantité de cortisol sécrété (principalement dépendant de la sensibilité du cortex surrénalien à l'ACTH), biodisponiblité de l'hormone et action tissulaire dépendant de l'efficacité des récepteurs et de leurs voies de signalisation. Cet article décrit la variabilité de la production de cortisol chez le Porc et sa relation avec l'adiposité des animaux et la qualité de la viande. Dans une deuxième partie, sont exposées les différentes approches utilisées pour trouver les gènes dont les polymorphismes expliquent cette variabilité génétique. Ceux-ci pourront être utilisés pour la sélection des animaux dont le phénotype corticotrope sera optimisé par rapport aux objectifs de production

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 »

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

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

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

Genetic Contribution to Initial and Progressive Alcohol Intake Among Recombinant Inbred Strains of Mice

We profiled individual differences in alcohol consumption upon initial exposure and during 5 weeks of voluntary alcohol intake in female mice from 39 BXD recombinant inbred strains and parents using the drinking in the dark (DID) method. In this paradigm, a single bottle of 20% (v/v) alcohol was presented as the sole liquid source for 2 or 4 h starting 3 h into the dark cycle. For 3 consecutive days mice had access to alcohol for 2 h followed by a 4th day of 4 h access and 3 intervening days where alcohol was not offered. We followed this regime for 5 weeks. For most strains, 2 or 4 h alcohol intake increased over the 5-week period, with some strains demonstrating greatly increased intake. There was considerable and heritable genetic variation in alcohol consumption upon initial early and sustained weekly exposure. Two different mapping algorithms were used to identify QTLs associated with alcohol intake and only QTLs detected by both methods were considered further. Multiple suggestive QTLs for alcohol intake on chromosomes (Chrs) 2, 6, and 12 were identified for the first 4 h exposure. Suggestive QTLs for sustained intake during later weeks were identified on Chrs 4 and 8. Thirty high priority candidate genes, including Entpd2, Per3, and Fto were nominated for early and sustained alcohol intake QTLs. In addition, a suggestive QTL on Chr 15 was detected for change in 2 h alcohol intake over the duration of the study and Adcy8 was identified as a strong candidate gene. Bioinformatic analyses revealed that early and sustained alcohol intake is likely driven by genes and pathways involved in signaling, and/or immune and metabolic function, while a combination of epigenetic factors related to alcohol experience and genetic factors likely drives progressive alcohol intake.Peer Reviewe

Network on « Genetics of adaptation and animal welfare »

Relations between genetics and animal welfare raise numerous questions as genetic characteristics are involved in many aspects of animals’ abilities to adapt to farming conditions, whether intensive or extensive. These questions are related to the genetic mechanisms of adaptation, to the consequences on animal welfare of the selection implemented up until now, and to the future improvements of the selection process. A network on the genetics of adaptation and animal welfare was built up within the multidisciplinary project “Agri Bien-être Animal” to review current knowledge. It aims also at providing usable references for regulatory discussions, as well as promoting synergies and exchanges between research units, development organisations and breeders.Les interrogations sur les relations entre génétique et bien-être des animaux sont d'autant plus nombreuses que les caractéristiques génétiques interviennent dans de nombreuses composantes des capacités d'adaptation des animaux à leurs conditions d'élevage, que celles-ci soient intensives ou extensives. Les questions portent à la fois sur les mécanismes génétiques de l'adaptation, les conséquences en matière de bien-être des sélections opérées jusqu'à présent et la conduite à tenir dans les futurs schémas de sélection. Un réseau Génétique de l'adaptation et bien-être a donc été créé au sein du programme interdisciplinaire INRA « Agri Bien-être Animal » pour faire le point des connaissances acquises. L'objectif est de fournir ainsi des références utilisables lors des discussions réglementaires et de faciliter les synergies et les échanges entre unités de recherche, organismes de développement et professionnels de la sélection

Methodologies for Assessing Disease Tolerance in Pigs

Features of intensive farming can seriously threaten pig homeostasis, well-being and productivity. Disease tolerance of an organism is the adaptive ability in preserving homeostasis and at the same time limiting the detrimental impact that infection can inflict on its health and performance without affecting pathogen burden per se. While disease resistance (DRs ) can be assessed measuring appropriately the pathogen burden within the host, the tolerance cannot be quantified easily. Indeed, it requires the assessment of the changes in performance as well as the changes in pathogen burden. In this paper, special attention is given to criteria required to standardize methodologies for assessing disease tolerance (DT) in respect of infectious diseases in pigs. The concept is applied to different areas of expertise and specific examples are given. The basic physiological mechanisms of DT are reviewed. Disease tolerance pathways, genetics of the tolerance-related traits, stress and disease tolerance, and role of metabolic stress in DT are described. In addition, methodologies based on monitoring of growth and reproductive performance, welfare, emotional affective states, sickness behavior for assessment of disease tolerance, and methodologies based on the relationship between environmental challenges and disease tolerance are considered. Automated Precision Livestock Farming technologies available for monitoring performance, health and welfare-related measures in pig farms, and their limitations regarding DT in pigs are also presented. Since defining standardized methodologies for assessing DT is a serious challenge for biologists, animal scientists and veterinarians, this work should contribute to improvement of health, welfare and production in pigs

Genotype on the Pigmentation Regulating PMEL17 Gene Affects Behavior in Chickens Raised Without Physical Contact with Conspecifics

Chickens homozygous for the Dominant white or wild-type allele of PMEL17 were subjected to a broad phenotyping in order to detect consistent differences between genotypes. To exclude feather pecking, the chickens were individually housed without physical contact, from the day of hatching, and tested for social, aggressive, fear and exploratory behaviors, and corticosterone and testosterone levels were assessed. In a principal component analysis, 53.2% of the behavior variation was explained by two factors. Factor one was an activity and social factor, and there was a significant effect of genotype on the factor scores. On factor two, related to aggressive behavior, there were significant effects of genotype, sex and their interaction. There were no genotype effects on hormone levels or any other measured non-behavioral phenotypes. Hence, differences in behavior between PMEL17 genotypes remained when negative social experiences were excluded, indicating a direct pleiotropic effect of the gene on behavior.The original publication is available at www.springerlink.com:Anna-Carin Karlsson, Pierre Mormede, Susanne Kerje and Per Jensen, Genotype on the Pigmentation Regulating PMEL17 Gene Affects Behavior in Chickens Raised Without Physical Contact with Conspecifics, 2011, BEHAVIOR GENETICS, (41), 2, 312-322.http://dx.doi.org/10.1007/s10519-010-9379-4Copyright: Springer Science Business Mediahttp://www.springerlink.com