HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Vidéo : Senseurs de marqueurs d'exposition - Identification des marqueurs non volatils
No full textImpossible de charger les vidéos de l'ANR SENTINEL qui sont publiés sur Youtube et sur le siteVidéo : Senseurs de marqueurs d'exposition - Identification des marqueurs non volatil
Livret des visuels d'interventions - Restitution des résultats du projet ANR SENTINEL
No full textLivret des visuels d'interventions - Webinaire de la restitution des résultats du projet ANR SENTINE
Inhibiting the fructose transporter GLUT5 boosts testosterone production in a murine mLTC-1 leydig cell line
No full textInternational audienceOver the past few decades, a significant change globally in sugar intake has coincided with a rising incidence of male infertility, which is now a major public health concern. Diets rich in fructose have been implicated in both male infertility and increased susceptibility to metabolic disorders, such as obesity, diabetes, and related heart problems. While fructose is known to be present in seminal fluid and crucial for sperm motility, the precise role of fructose in testicular function remains largely unknown.GLUT5 is an exclusive fructose transporter essential for dietary fructose uptake in the intestine. It is also expressed mainly in germ and Leydig cells. We recently revealed that disrupting the Glut5 gene in male mice impairs spermatogenesis and steroidogenesis. However, its specific role within Leydig cells remains unexplored. Therefore, we investigated its role by inhibiting GLUT5 in a murine Leydig cell line (mLTC-1) using a specific inhibitor of GLUT5, MSNBA, combined with a multi-omics approach.Exposing mLTC-1 cells to MSNBA reduced the intracellular fructose content, limited cell proliferation, and enhanced progesterone and androgens production (Δ4-androstenedione and testosterone). The latter was associated with the upregulation of two genes and proteins involved in steroidogenesis, such as Hsd3b and steroidogenic acute regulatory protein (StAR). GLUT5 inhibition in mLTC-1 cells also modified lipid and carbohydrate metabolism. Lipidomic analysis showed decreased cholesterol esters and a shift in the ratio of polyunsaturated fatty acids (PUFAs) to monounsaturated fatty acids (MUFAs). These lipid changes correlated with alterations in the expression of mRNA-encoding enzymes involved in lipogenesis, such as ELOVL6. Metabolomics analysis showed a reduction in most glycolysis metabolites, except for pyruvate and lactate. However, pyruvate could conserve its level by a production through an amino acid pathway using the higher branched-chain amino acid content. Nevertheless, the activity of mitochondria measured by seahorse was not altered. The transcriptomic analysis performed by BRB-seq approach revealed an upregulation of several androgen-sensitive genes, such as Akap5, Slc39a9, an androgen receptor or lactate dehydrogenase A (Ldha), which produces lactate, and downregulation of several genes associated with the insulin pathway such as Tsc2 or the hexokinase Hkdc1.In conclusion, GLUT5 supported fructose intake in the murine Leydig cell line mLTC-1, leading to a reduction in cell proliferation. The consequences of inhibition of GLUT5 led to an increase in fatty acids cell content, a perturbation in glycolysis and amino-acid metabolism but an enhanced androgen production. Since androgens regulate spermatogenesis, hyperandrogenism induced by a lower fructose content in Leydig cells may be a primary cause leading to the disruption of sperm production and quality, as well as sexual behavior, as described in the GLUT5 KO mouse model
Genetic Parameter Estimation for Plasma Biomarkers Associated With Energy Reserves During Critical Physiological Stages in Sheep
No full textInternational audienceThe ability of ruminants to mobilise and restore body reserves (BR) over time, referred to as BR dynamics, is currently considered an interesting biological component to be included in breeding programs targeting enhanced BR resilience. However, genetic studies of proxies for BR levels and BRD remain scarce, particularly in small ruminants. The aim of this study was to estimate the genetic parameters for key plasma biomarker concentrations in sheep at critical physiological stages (PhySt i.e., mating; mid‐pregnancy, before‐lambing, after‐lambing, and weaning), and their changes over time. Non‐esterified fatty acids (NEFA), β‐hydroxybutyrate (BHB), triiodothyronine (T3) and insulin (INS) were monitored at those PhySt in successive production cycles. A total of 659 productive Romane ewes were phenotyped for one ( n = 252, multiparous) or two ( n = 407, primiparous and multiparous) cycles. BR mobilisation was observed from the second half of pregnancy and during suckling while BR accretion was more evident from weaning until the next mid‐pregnancy. Considering biomarkers concentrations as repeated measurements through the whole production cycle, heritability estimates were 0.07, 0.09, 0.15, and 0.10 for NEFA, BHB, T3, and INS, respectively. Heritability estimates for plasma biomarkers at key PhySt ranged from 0.08 to 0.16 for NEFA, 0.07 to 0.12 for BHB, 0.09 to 0.18 for T3, and 0.04 to 0.15 for INS. Heritability estimates for biomarker changes over time ranged from 0.01 to 0.23. Genetic correlation estimates between different PhySt were positive for each plasma biomarker and ranged from 0.19 to 0.87 for NEFA, from 0.50 to 0.89 for BHB, from 0.54 to 0.95 for T3 and from 0.34 to 0.90 for INS. Most genetic correlation estimates between biomarkers at a given PhySt were generally low to moderate ( r g = −0.52 to 0.59), with few showing strong negative or positive values beyond 0.60 in magnitude. Considering changes over time, correlations were similarly low to moderate ( = −0.59 to 0.53), with only a few estimates reaching high values ( = −0.60 to −0.97 and 0.67 to 0.97). This study demonstrates that blood biomarkers related to energy BR have genetic variation, indicating their potential for implementation in sheep breeding programs aimed at improving BR use and build‐up
A comprehensive genome-wide scan for parent-of-origin expressed genes in the pig clarifies the conservation landscape of genomic imprinting
No full textInternational audienceBackground : Although next generation sequencing technologies enable nowadays to detect imprinted genes in a genome-wide manner, a wide spectrum of this phenomena is evaluated only in humans and rodents. Livestock species including artiodactyles are an important phylogenic clade within eutherians for which only few dedicated studies on specific genes have been performed. These species might represent important models for genomic imprinting with applications in various biological fields including evolution, molecular genetics and epigenetics and determinism of complex traits.Results : Here, we propose to map genes showing a parental expression bias in hypothalamus, muscle and placenta in piglets around birth using an extensive strategy that minimized biases and relied on reciprocal crosses, reconstruction of parental phases after imputation and statistical analyses discriminating parent-of-origin from allele-specific expression. We detected 141 genes with strong to exclusive parental expression bias (ratio above 25:75) including 51 with an exclusive parental expressed allele (ratio above 5:95). A large proportion (80%) of genes have never been shown to exhibit parent-of-origin expression and a small proportion (15%) are shared by at least two tissues, suggesting an overall weak conservation landscape of genomic imprinting. Interestingly, we identified novel parent-of-origin expressed genes involved in neurodevelopmental (PREPL, Prolyl Endopeptidase Like) and fetal growth (FAM20B, Glycosaminoglycan Xylosylkinase and POU6F2, POU Class 6 Homeobox 2) functions. In-depth analyses of specific loci highlighted specific imprinted isoforms of COPG2 (COPI Coat Complex Subunit Gamma 2) and confirmed livestock-specific imprinted genes such as zing finger proteins ZNF300 (Zinc Finger Protein 300-like gene) and ZNF791 (Zinc Finger Protein 791).Conclusions : Altogether, our results provide an atlas of parent-of-origin expressed genes in pig making it the most documented species for genomic imprinting after humans and rodents. Our findings indicate a weak conservation of this mechanism across species and tissues, suggesting a distinction between a small number of core imprinted genes shared across eutherians and others. These latter parent-of-origin expressed genes might be subjected to evolutionary forces that would determine their imprinting status either in a livestock-specific or tissue-specific manner
Évolution génétique de l'hémagglutinine des virus influenza A
No full textInfluenza viruses pose a threat to both animal and human health due to their high genetic variability and zoonotic potential. In birds, H5 and H7 subtypes can evolve into highly pathogenic forms capable of systemic replication. This evolution is characterized by the acquisition of a multibasic cleavage site (MBCS) in hemagglutinin (HA). The genetic mechanisms underlying this evolutionary process, as well as the observation that certain HA sequences may have an increased risk of acquiring such insertions, remain poorly understood.By combining experimental evolution and modeling approaches, we show that the thermodynamic stability of the product–template dimer encoding the HA cleavage site sequence is the main driver of nucleotide insertions in H5 and some H7 viruses. Specifically, certain sequences promote dissociation of the product–template dimer and its upstream reassociation, allowing the viral polymerase to backtrack and duplicate nucleotide segments.We developed a mathematical model based on the thermodynamic stability of the product–template dimer that accurately predicts the risk of MBCS acquisition through insertions. Using this predictive tool, we identified H5 and H7 sequences with an increased probability of acquiring insertions in the HA cleavage site, thus providing a sequence-based risk assessment strategy for early warning and targeted control measures.Finally, we investigated the role of recombination in the evolution of H5 viruses and concluded that this mechanism can occur in these viruses, even though, in our observations, it did not directly lead to the acquisition of a functional MBCS. Our results indicate that such recombination events systematically arise during cRNA synthesis, revealing a key step in the genomic plasticity of influenza viruses.Les virus influenza représentent une menace pour la santé animale et humaine en raison de leur forte variabilité génétique et de leur potentiel zoonotique. Chez les oiseaux, les virus des sous-types H5 et H7 peuvent évoluer vers des formes hautement pathogènes, capables de se répliquer de manière systémique. Cette évolution se caractérise par l’acquisition d’un site de clivage multibasique (MBCS) dans l’hémagglutinine (HA). Le mécanisme génétique sous-jacent à ce processus évolutif, ainsi que le fait que certaines séquences de HA puissent présenter un risque accru d’acquérir de telles insertions, demeurent encore mal compris.En combinant des approches d’évolution expérimentale et de modélisation, nous montrons que la stabilité thermodynamique du dimère produit-matrice codant pour la séquence du site de clivage HA est le principal moteur des insertions de nucléotides chez les virus H5 et certains virus H7. En effet, certaines séquences favorisent la dissociation du dimère produit-matrice et la réassociation en amont, permettant à la polymérase virale de reculer et de dupliquer des segments nucléotidiques.Nous avons développé un modèle mathématique basé sur la stabilité thermodynamique du dimère produit-matrice qui prédit avec précision le risque d’acquisition d’un MBCS via des insertions. Grâce à cet outil prédictif, nous avons identifié des séquences H5 et H7 présentant une probabilité accrue d’acquérir des insertions dans le site de clivage HA, proposant ainsi cette évaluation du risque basée sur la séquence comme stratégie de préalerte et de contrôle ciblé.Enfin, nous avons étudié le rôle de la recombinaison dans l’évolution des virus H5 et conclu que ce mécanisme est possible chez les virus H5, même si, dans nos observations, les recombinaisons n'ont pas directement conduit à l’acquisition d’un MBCS fonctionnel. Nos résultats indiquent que ces événements de recombinaison se produisent systématiquement lors de la synthèse du cRNA, révélant une étape clé de la plasticité génomique des virus influenza
Utilisation des Anticorps monoclonaux dans le cadre du traitement du Lupus érythémateux systémique : État des lieux en médecine humaine et perspective d’application en médecine vétérinaire
No full textSystemic lupus erythematosus is a complex and heterogeneous autoimmune disease. Despite significant advances in understanding its pathophysiology, conventional treatments still present many limitations. In recent years, biotherapies and particularly monoclonal antibodies, have emerged as promising targeted therapeutic alternatives, with encouraging clinical outcomes in human medicine. At the same time, forms of systemic lupus erythematosus have been described in pets, especially in dogs and more rarely in cats, with similar symptoms but limited therapeutic options. This manuscript provides an overview of the use of monoclonal antibodies in the treatment of human lupus and explores their potential applications in veterinary medicine, based on available data and the specific challenges involved in adapting such biotherapies to pets.Le Lupus érythémateux systémique est une maladie auto-immune complexe et hétérogène. Malgré des avancées notables dans la compréhension de sa physiopathologie, les traitements conventionnels présentent encore de nombreuses limites. Ces dernières années les biothérapies, et notamment les anticorps monoclonaux, ont émergé comme une alternative thérapeutique ciblée prometteuse, avec des résultats cliniques encourageants en médecine humaine. Parallèlement, des formes de lupus érythémateux systémique ont été décrites chez les animaux de compagnie, chez le chien et plus rarement chez le chat, avec des symptômes similaires mais un accès thérapeutique limité. Ce manuscrit dresse un état des lieux de l’utilisation des anticorps monoclonaux dans le traitement du lupus humain et explore leur potentiel d’application en médecine vétérinaire, en s’appuyant sur les données disponibles et les défis spécifiques à l’adaptation de ces biothérapies aux espèces animales
Draft genome and transcriptomic sequence data of three invasive insect species
No full textInternational audienceCydalima perspectalis (the box tree moth), Leptoglossus occidentalis (the western conifer seed bug), and Tecia solanivora (the Guatemalan tuber moth) are three economically harmful invasive insect species. This study presents their genomic and transcriptomic sequences, generated through whole-genome sequencing, RNA-seq transcriptomic data, and Hi-C sequencing. The resulting genome assemblies exhibit good quality, providing valuable insights into these species. The genome sizes are 500.4 Mb for C. perspectalis , 1.74 Gb for L. occidentalis , and 623.3 Mb for T. solanivora . These datasets are available in the NCBI Sequence Read Archive (BioProject PRJNA1140410) and serve as essential resources for population genomics studies and the development of effective pest management strategies, addressing significant gaps in the understanding of invasive insect species
Analysis of Polycerate Mutants Reveals the Evolutionary Co-option of HOXD1 to Determine the Number and Topology of Horns in Bovidae
No full textInternational audienceIn the course of evolution, pecorans (i.e. higher ruminants) developed a remarkable diversity of osseous cranial appendages, collectively referred to as ‘headgear’, which likely share the same origin and genetic basis. However, the nature and function of the genetic determinants underlying their number and position remain elusive. Jacob and other rare populations of sheep and goats, are characterized by polyceraty, the presence of more than two horns. Here, we characterize distinct POLYCERATE alleles in each species, both associated with defective HOXD1 function. We show that haploinsufficiency at this locus results in the splitting of horn bud primordia, likely following the abnormal extension of an initial morphogenetic field. These results highlight the key role played by this gene in headgear patterning and illustrate the evolutionary co-option of a gene involved in the early development of bilateria to properly fix the position and number of these distinctive organs of Bovidae
