Effect of metabolically divergent pig breeds and tissues on mesenchymal stem cell expression patterns during adipogenesis.

BACKGROUND: Unraveling the intricate and tightly regulated process of adipogenesis, involving coordinated activation of transcription factors and signaling pathways, is essential for addressing obesity and related metabolic disorders. The molecular pathways recruited by mesenchymal stem cells (MSCs) during adipogenesis are also dependent on the different sources of the cells and genetic backgrounds of donors, which contribute to the functional heterogeneity of the stem cells and consequently affect the developmental features and fate of the cells. METHODS: In this study, the alteration of transcripts during differentiation of synovial mesenchymal stem cells (SMSCs) derived from fibrous synovium (FS) and adipose synovial tissue (FP) of two pig breeds differing in growth performance (German Landrace (DL)) and fat deposition (Angeln Saddleback (AS)) was investigated. SMSCs from both tissues and breeds were stimulated to differentiate into adipocytes in vitro and sampled at four time points (day 1, day 4, day 7 and day 14) to obtain transcriptomic data. RESULTS: We observed numerous signaling pathways related to the cell cycle, cell division, cell migration, or cell proliferation during early stages of adipogenesis. As the differentiation process progresses, cells begin to accumulate intracellular lipid droplets and changes in gene expression patterns in particular of adipocyte-specific markers occur. PI3K-Akt signaling and metabolic pathways changed most during adipogenesis, while p53 signaling and ferroptosis were affected late in adipogenesis. When comparing MSCs from FS and FP, only a limited number of differentially expressed genes (DEGs) and enriched signaling pathways were identified. Metabolic pathways, including fat, energy or amino acid metabolism, were highly enriched in the AS breed SMSCs compared to those of the DL breed, especially at day 7 of adipogenesis, suggesting retention of the characteristic metabolic features of their original source, demonstrating donor memory in culture. In contrast, the DL SMSCs were more enriched in immune signaling pathways. CONCLUSIONS: Our study has provided important insights into the dynamics of adipogenesis and revealed metabolic shifts in SMSCs associated with different cell sources and genetic backgrounds of donors. This emphasises the critical role of metabolic and genetic factors as important indications and criteria for donor stem cell selection.

Multi-tissue gene expression profiling of cows with a genetic predisposition for low and high milk urea levels.

Milk urea (MU) concentration is proposed as an indicator trait for breeding toward reduced nitrogen (N) emissions and leaching in dairy. We selected 20 German Holstein cows based on MU breeding values, with 10 cows each having low (LMUg) and high (HMUg) MU genetic predisposition. Using RNA-seq, we characterized these cows to unravel molecular pathways governing post-absorptive body N pools focusing on renal filtration and reabsorption of nitrogenous compounds, hepatic urea formation and mammary gland N excretion. While we observed minor adjustments in cellular energy metabolism in different tissues associated with different MU levels, no transcriptional differences in liver ammonia detoxification were detected, despite significant differences in MU between the groups. Differential expression of AQP3 and SLC38A2 in the kidney provides evidence for higher urea concentration in the collecting duct of LMU cows than HMU cows. The mammary gland exhibited the most significant differences, particularly in tricarboxylic acid (TCA) cycle genes, amino acid transport, tRNA binding, and casein synthesis. These findings suggest that selecting for lower MU could lead to altered urinary urea (UU) handling and changes in milk protein synthesis. However, given the genetic variability in N metabolism components, the long-term effectiveness of MU-based selection in reducing N emissions remains uncertain.

Exposure to artificial ultraviolet-B light mediates alterations on the hepatic transcriptome and vitamin D metabolism in pigs.

In the currently prevailing pig husbandry systems, the vitamin D status is almost exclusively dependent on dietary supply. Additional endogenous vitamin D production after exposure to ultraviolet-B (UVB) light might allow the animals to utilize minerals in a more efficient manner, as well as enable the production of functional vitamin D-enriched meat for human consumption. In this study, growing pigs (n = 16) were subjected to a control group or to a daily narrowband UVB exposure of 1 standard erythema dose (SED) for a period of 9 weeks until slaughter at a body weight of 105 kg. Transcriptomic profiling of liver with emphasis on the associated effects on vitamin D metabolism due to UVB exposure were evaluated via RNA sequencing. Serum was analyzed for vitamin D status and health parameters such as minerals and biochemical markers. The serum concentration of calcidiol, but not calcitriol, was significantly elevated in response to UVB exposure after 17 days on trial. No effects of UVB exposure were observed on growth performance and blood test results. At slaughter, the RNA sequencing analyses following daily UVB exposure revealed 703 differentially expressed genes (DEGs) in liver tissue (adjusted p-value < 0.01). Results showed that molecular pathways for vitamin D synthesis (CYP2R1) rather than cholesterol synthesis (DHCR7) were preferentially initiated in liver. Gene enrichment (p < 0.05) was observed for reduced cholesterol/steroid biosynthesis, SNARE interactions in vesicular transport, and CDC42 signaling. Taken together, dietary vitamin D supply can be complemented via endogenous production after UVB exposure in pig husbandry, which could be considered in the development of functional foods.

Jejunal microbiota of broilers fed varying levels of mineral phosphorus.

Efforts to achieve sustainable phosphorus (P) inputs in broiler farming which meet the physiological demand of animals include nutritional intervention strategies that have the potential to modulate and utilize endogenous and microbiota-associated capacities. A temporal P conditioning strategy in broiler nutrition is promising as it induces endocrinal and transcriptional responses to maintain mineral homeostasis. In this context, the current study aims to evaluate the composition of the jejunal microbiota as a functional entity located at the main absorption site involved in nutrient metabolism. Starting from a medium or high P supply in the first weeks of life of broilers, a depletion strategy was applied at growth intervals from d 17 to 24 and d 25 to 37 to investigate the consequences on the composition of the jejunal microbiota. The results on fecal mineral P, calcium (Ca), and phytate contents showed that the diets applied to the depleted and non-depleted cohorts were effective. Microbial diversity in jejunum was represented by alpha diversity indices which appeared unaffected between dietary groups. However, chickens assigned to the dietary P depletion groups showed significantly higher abundances of Facklamia, Lachnospiraceae, and Ruminococcaceae compared to non-depleted control groups. Based on current knowledge of microbial function, these microorganisms make only a minor contribution to the birds' adaptive mechanism in the jejunum following P depletion. Microbial taxa such as Brevibacterium, Brachybacterium, and genera of the Staphylococcaceae family proliferated in a P-enriched environment and might be considered biomarkers for excessive P supply in commercial broiler chickens.

Stepwise Reduction of Dietary Phosphorus in Diets for Piglets and Fattening Pigs of Different Genetic Origin Housed under Various Station Environments-A Ringtest.

The reduction of emissions of nutrients from livestock is one of the main topics in areas with intensive animal husbandry. In order to minimize the loss of nutrients into the environment, it is common practice to feed animals as close as possible to metabolic demands. For phosphorus (P), there are various studies for swine and poultry, which showed that a reduction of dietary P levels is possible, if a sufficient level of phytase is added to the diet. The supplementation of a sufficient dosage of phytase to plant-based diets leads to an increase in digestible phosphorus (dP) upon the hydrolisation of phytate (InsP6) to P and lower inositol-phosphates. However, most of these studies were conducted under standardized experimental conditions. In terms of transfer to practical conditions with varying housing, management and genetics, there are concerns that have led to speculation by farmers and veterinarians whether the reduction of dietary P could negatively affect bone health and therefore animal welfare. In order to test whether a reduction of dietary P according to the recommendations for dP of the German Society of Nutrition Physiology (GfE) affects bone mineralization and growth performance, a ringtest was conducted where piglets and fattening pigs were fed at four experimental stations with three centrally produced diets from the same batches. The diets contained three different levels of P and were designed to reflect practical diets. The P level decreased from diet one to three, respectively. Diets one and two were calculated to contain P levels, which are typically fed under practical conditions in Germany. The third diet was optimized to fulfill the requirements of dP by the GfE. The animals were fed in two phases as post-weaning piglets (8-15 kg and 15-28 kg BW) followed by a three-phase fattening regime (28-60 kg, 60-90 kg and 90-120 kg BW). Individual body weight and feed consumption (pen basis or individually, depending on the experimental station) were recorded for every feeding phase. At the end of the experiment, animals were slaughtered. At one experimental station, additional blood serum, metatarsi of the left leg and kidney tissue were sampled to analyze serum P concentration, expression of P transporters in the kidney and bone traits. In two experimental stations, femur and vertebra were sampled, and bone ash was determined. Overall, animal performance and all other traits analyzed did not differ between the treatment with the highest and the treatment with the lowest dietary P concentration. The results demonstrate that it is possible to decrease dietary P according to the recommendations for dP of the GfE, without impairing the animals' performance or mineral homeostasis and health. A reduction of total P by reducing mineral P to the levels of the present study require the supplementation of phytase to achieve sufficient concentrations of dP.

RNA-Seq-based discovery of genetic variants and allele-specific expression of two layer lines and broiler chicken.

Recent advances in the selective breeding of broilers and layers have made poultry production one of the fastest-growing industries. In this study, a transcriptome variant calling approach from RNA-seq data was used to determine population diversity between broilers and layers. In total, 200 individuals were analyzed from three different chicken populations (Lohmann Brown (LB), n = 90), Lohmann Selected Leghorn (LSL, n = 89), and Broiler (BR, n = 21). The raw RNA-sequencing reads were pre-processed, quality control checked, mapped to the reference genome, and made compatible with Genome Analysis ToolKit for variant detection. Subsequently, pairwise fixation index (F ST) analysis was performed between broilers and layers. Numerous candidate genes were identified, that were associated with growth, development, metabolism, immunity, and other economically significant traits. Finally, allele-specific expression (ASE) analysis was performed in the gut mucosa of LB and LSL strains at 10, 16, 24, 30, and 60 weeks of age. At different ages, the two-layer strains showed significantly different allele-specific expressions in the gut mucosa, and changes in allelic imbalance were observed across the entire lifespan. Most ASE genes are involved in energy metabolism, including sirtuin signaling pathways, oxidative phosphorylation, and mitochondrial dysfunction. A high number of ASE genes were found during the peak of laying, which were particularly enriched in cholesterol biosynthesis. These findings indicate that genetic architecture as well as biological processes driving particular demands relate to metabolic and nutritional requirements during the laying period shape allelic heterogeneity. These processes are considerably affected by breeding and management, whereby elucidating allele-specific gene regulation is an essential step towards deciphering the genotype to phenotype map or functional diversity between the chicken populations. Additionally, we observed that several genes showing significant allelic imbalance also colocalized with the top 1% of genes identified by the FST approach, suggesting a fixation of genes in cis-regulatory elements.

Transcriptome changes during osteogenesis of porcine mesenchymal stem cells derived from different types of synovial membranes and genetic background.

Synovial membrane mesenchymal stem cells (SMSCs) often serve as in vitro model for bone disease, but the molecular mechanisms driving osteogenesis in SMSCs from different donor cells of various sources and breeds remain unclear. In this study, porcine SMSCs isolated from adipose synovium (FP) and fibrous synovium (FS) of Angeln Saddleback (AS) and German Landrace (DL) were used to discover the signaling network change after osteogenic induction. During osteogenic differentiation, mineral deposition was first observed at day 14 and further increased until day 21. Transcriptional changes between day 1 and day 21 were enriched in several signaling pathways, including Wnt, PI3K-Akt, and TGF-beta pathway. Certain pathways related to osteogenesis, including osteoblast differentiation, regulation of bone mineralization, and BMP signaling pathway, were enriched at late time points, as confirmed by the osteogenic markers ALPL, COL1A1, and NANOG. A fraction of differentially expressed genes (DEGs) were found between FP and FS, while DEGs between AS and DL increased during the differentiation phase until day 7 and then decreased from day 14 to day 21. These genes are involved in several important signaling pathways, including TGF-beta, Wnt, and lipid-related signaling pathways, suggesting that SMSCs from these two breeds have different osteogenic capabilities.

Efficacy of dietary vitamin D3 and 25(OH)D3 on reproductive capacities, growth performance, immunity and bone development in pigs.

Vitamin D3 (Vit D3) and 25(OH)D3 are used as dietary sources of active vitamin D (1,25(OH)2D3) in pig husbandry. Although acting primarily on intestine, kidney and bone, their use in pig nutrition has shown a wide range of effects also in peripheral tissues. However, there is an ambiguity in the existing literature about whether the effects of Vit D3 and 25(OH)D3 differ in attributing the molecular and phenotypic outcomes in pigs. We searched Web of Science and PubMed databases concerning the efficacy of Vit D3 in comparison with 25(OH)D3 on pig physiology, i.e. reproductive capacities, growth performance, immunity and bone development. Dietary intake of Vit D3 or 25(OH)D3 did not influence the reproductive capacity of sows. Unlike Vit D3, the maternal intake of 25(OH)D3 significantly improved the growth performance of piglets, which might be attributed to maternally induced micronutrient efficiency. Consequently, even in the absence of maternal vitamin D supplementation, 25(OH)D3-fed offspring also demonstrated better growth than the offspring received Vit D3. Moreover, a similar superior impact of 25(OH)D3 was seen with respect to serum markers of innate and humoral immunity. Last but not least, supplements containing 25(OH)D3 were found to be more effective than Vit D3 to improve bone mineralisation and formation, especially in pigs receiving basal diets low in Ca and phosphorus. The insights are of particular value in determining the principal dietary source of vitamin D to achieve its optimum utilisation efficiency, nutritional benefits and therapeutic potency and to further improve animal welfare across different management types.

Air-liquid interface cultures trigger a metabolic shift in intestinal epithelial cells (IPEC-1).

An improved oxygen availability in air-liquid interface (ALI) cultures of enterocytes of the small intestine seems to be primarily responsible for morphological, metabolic, and functional changes. Intestinal porcine epithelial cells 1 (IPEC-1) are less investigated and are rarely used as model for intestinal barrier but showed a profound change of cell shape during ALI cultivation. We aim to answer the following question: Are the observed morphological effects accompanied by changes in metabolic function? A microarray analysis of submerged culture (SMC) and ALI cultures identified 830 significantly regulated genes. Subsequent functional clustering revealed alterations in 31 pathways, with the highest number of regulated genes in metabolic pathways, carbon metabolism, glycolysis, and hypoxia-inducible factor (HIF) signaling. Furthermore, HIF-1α as a mediator of a metabolic switch between glycolysis and oxidative phosphorylation showed a trend of increased mRNA levels in ALI in contrast to a reduced nuclear HIF-1α content in the nucleus. Candidate genes of oxidative phosphorylation such as a mitochondrial marker exhibited enhanced mRNA levels, which was confirmed by western blot analysis. Cytochrome C oxidase (COX) subunit 5B protein was decreased in ALI, although mRNA level was increased. The oxidation of ferrocytochrome C to ferricytochrome C was used for detection of cytochrome C oxidase activity of isolated mitochondria and resulted in a trend of higher activity in ALI. Furthermore, quantification of glucose and lactate concentrations in cell culture medium revealed significantly reduced glucose levels and decreased lactate production in ALI. To evaluate energy metabolism, we measured cellular adenosine triphosphate (ATP) aggregation in homogenized cell suspensions showing similar levels. However, application of the uncoupling agent FCCP reduced ATP levels in ALI but not in SMC. In contrast, blocking with 2-desoxy-D-glucose (2DG) significantly reduced ATP content in ALI and SMC. These results indicate a metabolic shift in IPEC-1 cultured under ALI conditions enhancing oxidative phosphorylation and suppressing glycolysis.

The dynamics of molecular, immune and physiological features of the host and the gut microbiome, and their interactions before and after onset of laying in two hen strains.

Aggregation of data, including deep sequencing of mRNA and miRNA data in jejunum mucosa, abundance of immune cells, metabolites, or hormones in blood, composition of microbiota in digesta and duodenal mucosa, and production traits collected along the lifespan, provides a comprehensive picture of lifelong adaptation processes. Here, respective data from two laying hen strains (Lohmann Brown-Classic (LB) and Lohmann LSL-Classic (LSL) collected at 10, 16, 24, 30, and 60 wk of age were analyzed. Data integration revealed strain- and stage-specific biosignatures, including elements indicative of molecular pathways discriminating the strains. Although the strains performed the same, they differed in the activity of immunological and metabolic functions and pathways and showed specific gut-microbiota-interactions in different production periods. The study shows that both strains employ different strategies to acquire and maintain their capabilities under high performance conditions, especially during the transition phase. Furthermore, the study demonstrates the capacity of such integrative analyses to elucidate molecular pathways that reflect functional biodiversity. The bioinformatic reduction of the multidimensional data provides good guidance for further manual review of the data.

Broiler physiological response to low phosphorus diets at different stages of production.

Phosphorus (P) inclusion in broiler diets needs to meet the physiological demands at a specific developmental stage to ensure the performance, health, and welfare of the birds and minimize nutrient losses. Toward a more efficient utilization of P in broiler husbandry, a timed nutritional conditioning strategy might enhance the endogenous mechanisms of mineral homeostasis and thus reduce dietary P supply of mineral sources. In this study, following a variable P supply in the starter phase, the effects of a dietary P depletion of broiler chickens were investigated at different developmental stages. Physiological adaptation mechanisms were elucidated based on zootechnical performance, endocrine parameters, regulation of intestinal P transport, bone characteristics, and health aspects. The results revealed a marked response to P depletion at the earliest developmental phase, after which indications of effective compensatory mechanism were detectable with advancing ages. Potential mechanisms that enable broilers to maintain mineral homeostasis primarily include endocrine control mediated by calcitriol actions, as well as intestinal P uptake and mineral mobilization from the bone. Conclusively, the precise timing, duration, and extent of a P depletion strategy in the broiler chicken might be considered for optimized nutrient utilization.

Intrinsic challenges of neonatal adaptation in swine.

The losses of piglets in commercial pig farming remain at concerning levels and need to be addressed through the implementation of new sustainable breeding and management strategies. In fact, piglets are especially at risk in the first days of life. Both genetics and the farrowing process have been shown to impact piglet vitality. In addition, knowledge of the animal-intrinsic responses in adapting to extra-uterine life is particularly important but is scarcely described in the scientific literature. In this review, the three phases that constitute neonatal adaptation in the pig are systematically presented. The first phase of early adaptation involves primarily the development of cardiorespiratory function (within the first 10 min of life) as well as thermoregulatory processes and acid-base balance (up to 24 h of life). In the second phase, homeostasis is established, and organ maturation takes place (up to 14 d post natum). The final third phase aims at the development of neurological, immunological and muscular features (up to 28 d of life). The involvement of aggravating and ameliorating factors such as dystocia, low colostrum yield and heat supply is key to the development of strategies to reduce piglet losses and increase vitality. The insights are of particular value in addressing current concerns in pig farming and to further improve animal welfare in pig production across different management types.

Prenatal transcript levels and metabolomics analyses reveal metabolic changes associated with intrauterine growth restriction and sex.

The metabolic changes associated with intrauterine growth restriction (IUGR) particularly affect the liver, which is a central metabolic organ and contributes significantly to the provision of energy and specific nutrients and metabolites. Therefore, our aim was to decipher and elucidate the molecular pathways of developmental processes mediated by miRNAs and mRNAs, as well as the metabolome in fetal liver tissue in IUGR compared to appropriate for gestational age groups (AGA). Discordant siblings representing the extremes in fetal weight at day 63 post conception (dpc) were selected from F2 fetuses of a cross of German Landrace and Pietrain. Most of the changes in the liver of IUGR at midgestation involved various lipid metabolic pathways, both on transcript and metabolite levels, especially in the category of sphingolipids and phospholipids. Differentially expressed miRNAs, such as miR-34a, and their differentially expressed mRNA targets were identified. Sex-specific phenomena were observed at both the transcript and metabolite levels, particularly in male. This suggests that sex-specific adaptations in the metabolic system occur in the liver during midgestation (63 dpc). Our multi-omics network analysis reveals interactions and changes in the metabolic system associated with IUGR and identified an important biosignature that differs between IUGR and AGA piglets.

Tissue-Wide Expression of Genes Related to Vitamin D Metabolism and FGF23 Signaling following Variable Phosphorus Intake in Pigs.

Calcium (Ca) and phosphorus (P) homeostasis is maintained by several regulators, including vitamin D and fibroblast growth factor 23 (FGF23), and their tissue-specific activation and signaling cascades. In this study, the tissue-wide expression of key genes linked to vitamin D metabolism (CYP2R1, CYP27A1, CYP27B1, CYP24A1, GC, VDR) and FGF23 signaling (FGF23, FGFR1-4, KL) were investigated in pigs fed conventional (trial 1) and divergent P diets (trial 2). The tissue set comprised kidney, liver, bone, lung, aorta, and gastrointestinal tract sections. Expression patterns revealed that non-renal tissues and cells (NRTC) express genes to form active vitamin D [1,25(OH)2D3] according to site-specific requirements. A low P diet resulted in higher serum calcitriol and increased CYP24A1 expression in the small intestine, indicating local suppression of vitamin D signaling. A high P diet prompted increased mRNA abundances of CYP27B1 for local vitamin D synthesis, specifically in bone. For FGF23 signaling, analyses revealed ubiquitous expression of FGFR1-4, whereas KL was expressed in a tissue-specific manner. Dietary P supply did not affect skeletal FGF23; however, FGFR4 and KL showed increased expression in bone at high P supply, suggesting regulation to balance mineralization. Specific NRTC responses influence vitamin D metabolism and P homeostasis, which should be considered for a thrifty but healthy P supply.

The Growth Performance, Nutrient Digestibility, Gut Bacteria and Bone Strength of Broilers Offered Alternative, Sustainable Diets Varying in Nutrient Specification and Phytase Dose.

This study assessed the use of locally sourced sustainable feed ingredients, rapeseed meal (RSM) and maize dried distiller grains with solubles (DDGS) in diets over traditional ingredients on the growth performance, bone strength and nutrient digestibility of broilers. This work also investigated the effects of supplementing exogenous phytase in two doses (500 vs. 1500 FTU/kg). Using male Ross 308 chicks (n = 320) assigned to receive one of four experimental diets: (1) Positive control diet 1 (PC1), a wheat, soya-based diet + 500 FTU/kg phytase. (2) Positive control diet 2, RSM/DDGS diet + 500 FTU/kg phytase (PC2). (3) Negative control (NC) reduced nutrient RSM/DDGS diet, no phytase. (4) The NC diet plus 1500 FTU/kg phytase (NC+). PC1 birds displayed higher feed intake and body weight gain consistently throughout the trial (p < 0.001) as well as increased body weight by 28 d and 42 d (p < 0.001). Whole-body dual emission X-ray absorptiometry (DXA) analysis revealed PC1 birds also had higher bone mineral density (BMD), bone mineral content (BMC), total bone mass, total lean mass and total fat mass than birds offered other treatments (p < 0.01). Diet had no significant effect on bone strength. Phytase superdosing improved the digestibility of dry matter (DM), neutral detergent fibre (NDF), gross energy (GE), calcium (Ca), potassium (K) and magnesium (Mg) compared to birds in other treatment groups. The phytase superdose also improved performance in comparison to birds offered the NC diet. Phytase superdosing increased the IP6 and IP5 degradation and increased the ileal inositol concentration of the birds. N excretion was lower for birds offered the traditional wheat−soya diet and highest for those offered the high-specification RSM/DDGS diet with a commercial dose of phytase. The addition of a phytase superdose to the negative control diet (NC+) reduced P excretion of birds by 15% compared to birds offered NC.

Genetic regulation and variation of expression of miRNA and mRNA transcripts in fetal muscle tissue in the context of sex, dam and variable fetal weight.

BACKGROUND: Impaired skeletal muscle growth in utero can result in reduced birth weight and pathogenesis of intrauterine growth restriction. Fetal and placental growth is influenced by many factors including genetic, epigenetic and environmental factors. In fact, the sex and genotype of the fetus itself, as well as the mother providing it with a suitable environment, influence the growth of the fetus. Hence, our goal was to decipher and elucidate the molecular pathways of developmental processes mediated by miRNAs and mRNAs in fetal muscle tissue in the context of sex, dam, and fetal weight. Therefore, we analyse the variation of miRNA and mRNA expression in relation to these factors. In addition, the coincidence of genetic regulation of these mRNAs and miRNAs, as revealed by expression quantitative trait loci (eQTL) analyses, with sex-, mother- and weight-associated expression was investigated. METHODS: A three-generation pig F2 population (n = 118) based on reciprocal crossing of German Landrace (DL) and Pietrain (Pi) was used. Genotype information and transcriptomic data (mRNA and miRNA) from longissimus dorsi muscle (LDM) of pig fetuses sampled at 63 days post-conception (dpc) were used for eQTL analyses. RESULTS: The transcript abundances of 13, 853, and 275 probe-sets were influenced by sex, dam and fetal weight at 63 dpc, respectively (FDR < 5%). Most of significant transcripts affected by sex were located on the sex chromosomes including KDM6A and ANOS1 or autosomes including ANKS1B, LOC100155138 and miR-153. The fetal muscle transcripts associated with fetal weight indicated clearer metabolic directions than maternally influenced fetal muscle transcripts. Moreover, coincidence of genetic regulation (eQTL) and variation in transcript abundance due to sex, dam and fetal weight were identified. CONCLUSIONS: Integrating information on eQTL, sex-, dam- and weight-associated differential expression and QTL for fetal weight allowed us to identify molecular pathways and shed light on the basic biological processes associated with differential muscle development in males and females, with implications for adaptive fetal programming.

Multi-Omics Reveals Different Strategies in the Immune and Metabolic Systems of High-Yielding Strains of Laying Hens.

Lohmann Brown (LB) and Lohmann Selected Leghorn (LSL) are two commercially important laying hen strains due to their high egg production and excellent commercial suitability. The present study integrated multiple data sets along the genotype-phenotype map to better understand how the genetic background of the two strains influences their molecular pathways. In total, 71 individuals were analyzed (LB, n = 36; LSL, n = 35). Data sets include gut miRNA and mRNA transcriptome data, microbiota composition, immune cells, inositol phosphate metabolites, minerals, and hormones from different organs of the two hen strains. All complex data sets were pre-processed, normalized, and compatible with the mixOmics platform. The most discriminant features between two laying strains included 20 miRNAs, 20 mRNAs, 16 immune cells, 10 microbes, 11 phenotypic traits, and 16 metabolites. The expression of specific miRNAs and the abundance of immune cell types were related to the enrichment of immune pathways in the LSL strain. In contrast, more microbial taxa specific to the LB strain were identified, and the abundance of certain microbes strongly correlated with host gut transcripts enriched in immunological and metabolic pathways. Our findings indicate that both strains employ distinct inherent strategies to acquire and maintain their immune and metabolic systems under high-performance conditions. In addition, the study provides a new perspective on a view of the functional biodiversity that emerges during strain selection and contributes to the understanding of the role of host-gut interaction, including immune phenotype, microbiota, gut transcriptome, and metabolome.

Jejunal transcriptomic profiling of two layer strains throughout the entire production period.

The jejunum plays crucial roles for the digestion and absorption of nutrients and minerals and for barrier functions that are essential for a healthy, productive life cycle of farm animals, including laying hens. Accordingly, knowledge of the molecular pathways that emerge in the intestine during development, and particularly at the beginning of laying activity, will help to derive strategies for improving nutrient efficiency in laying hens. In this study, jejunal samples were obtained from two high-yielding layer strains at five developmental stages (weeks 10, 16, 24, 30 and 60 of life) for RNA-sequencing, alongside the profiling of blood plasma parameters to approximate the dynamics of mineral homeostasis. The results reflected a marked distinction between the pre-laying and laying phase as inferred from levels of parathyroid hormone, triiodothyronine, estradiol, vitamin D, and calcium. Moreover, the expression patterns of the intestinal mucosa responded directly to the changing metabolic and nutritional profiles at the beginning of the laying phase in maturing high-yielding strains of laying hens. These comprise signaling events namely RANK/RANKL signaling and cellular senescence. Taken together, the timing of sexual maturity of laying hens demands closer examination to unravel metabolic requirements and associated endogenous mechanisms.

Identification of Genomic Regions Influencing N-Metabolism and N-Excretion in Lactating Holstein- Friesians.

Excreted nitrogen (N) of dairy cows contribute to environmental eutrophication. The main N-excretory metabolite of dairy cows is urea, which is synthesized as a result of N-metabolization in the liver and is excreted via milk and urine. Genetic variation in milk urea (MU) has been postulated but the complex physiology behind the trait as well as the tremendous diversity of processes regulating the N-metabolism impede the consistent determination of causal regions in the bovine genome. In order to map the genetic determinants affecting N-excretion, MU and eight other N-excretory metabolites in milk and urine were assessed in a genome-wide association study. Therefore phenotypes of 371 Holstein- Friesians were obtained in a trial on a dairy farm under near commercial conditions. Genotype data comprised SNP information of the Bovine 50K MD Genome chip (45,613 SNPs). Significantly associated genomic regions for MU concentration revealed GJA1 (BTA 9), RXFP1, and FRY1 (both BTA 12) as putative candidates. For milk urea yield (MUY) a promising QTL on BTA 17 including SH3D19 emerged, whereas RCAN2, CLIC5, ENPP4, and ENPP5 (BTA 23) are suggested to influence urinary urea concentration. Minor N-fractions in milk (MN) may be regulated by ELF2 and SLC7A11 (BTA 17), whilst ITPR2 and MYBPC1 (BTA 5), STIM2 (BTA 6), SGCD (BTA 7), SLC6A2 (BTA 18), TMCC2 and MFSD4A (BTA 16) are suggested to have an impact on various non-urea-N (NUN) fractions excreted via urine. Our results highlight genomic regions and candidate genes for N-excretory metabolites and provide a deeper insight into the predisposed component to regulate the N-metabolism in dairy cows.