Project description:Weaning is a very critical period for piglets, typically accompanied by lower feed intake, weight loss after weaning and increased mortality. At weaning, piglets are exposed to many stressors, such as loss of mothering, mixing with other litters, end of lactational immunity, and a change in their environment and gut microbiota. After weaning, morphological and histological changes occur in the small intestine of piglets producing a rapid change of feeding regime which is critical for the immature digestive system. Sixteen female piglets were weaned to assess the effect of sorbic acid supplementation on the small intestine tissue transcriptome. At weaning day (T0), 4 piglets were sacrified and tissue samples collected. The remaining 12 piglets were weighted and randomly assigned to different post weaning (T5) diets. Diet A (n=6) contained 5 g/kg of sorbic acid. Diet B (n=6) is the same as Standard diet. Total RNA was isolated from ileum samples to be analyzed using the a CombiMatrix CustomArrayTM 90K platform . Even though diet had no detectable effect during the first 5 days after weaning, outcomes from this study highlighted some of the response mechanisms to the stress of weaning occurring in the piglet gut. A total of 205 differentially expressed genes were used for functional analysis using bioinformatics through BLAST2GO, Ingenuity Pathway Analysis 8.0, and the Dynamic Impact Aproach (DIA). Bioinformatics analysis revealed that Apoptosis, RIG-I-like and NOD-like receptor signaling were altered as a result of weaning. Results suggest that immune and inflammatory responses were activated and likely are a cause of small intestine atrophy as revealed by a decrease in villus height and villus/crypt ratio. Keywords: weaning, gut, gene expression, sorbic acid, microarray analysis
Project description:Background: Poor nutrition during development programs kidney function. No studies on postnatal consequences of decreased perinatal nutrition exist in nonhuman primates (NHP) for translation to human renal disease. Our baboon model of moderate maternal nutrient restriction (MNR) produces intrauterine growth restricted (IUGR) and programs renal fetal phenotype. We hypothesized that the IUGR phenotype persists postnatally influencing responses to a high-fat, high-carbohydrate, high-salt (HFCS) diet. Methods: Pregnant baboons ate chow Control (CON) or 70% of control intake (MNR) from 0.16 gestation through lactation. MNR offspring were IUGR at birth. At weaning, all offspring, (control and IUGR females and males n=3/group) ate chow. At ~3.5 years age, blood, urine, and kidney biopsies were collected before and after a 7-week high HFCS diet challenge. Kidney function, unbiased kidney gene expression, and untargeted urine metabolomics were evaluated. Results: IUGR female and male kidney transcriptome and urine metabolome differed from CON at 3.5 years, prior to HFCS. After the challenge, we observed sex-specific and fetal exposure-specific responses in urine creatinine, urine metabolites, and renal signaling pathways. Conclusions: We previously showed mTOR signaling dysregulation in IUGR fetal kidneys. Before HFCS, gene expression analysis indicated that dysregulation persists postnatally in IUGR females. IUGR male offspring response to HFCS showed uncoordinated signaling pathway responses suggestive of proximal tubule injury. To our knowledge, this is the first study comparing CON and IUGR postnatal juvenile NHP and the impact of fetal and postnatal life caloric mismatch. Perinatal history needs to be taken into account when assessing renal disease risk.
Project description:MicroRNAs (miRNAs) play important roles in intestinal diseases; however, the role of miRNAs during weaning stress is unknown. In our study, six jejunal small RNA libraries constructed from weaning piglets at 1, 4 and 7 d after weaning (libraries W1, W4 and W7, respectively) and from suckling piglets on the same days as the weaning piglets (libraries S1, S4 and S7, respectively) were sequenced using Solexa high-throughput sequencing technology. Overall, 260 known swine miRNAs and 317 novel candidate miRNA precursors were detected in the six libraries. The results revealed that 16 differentially expressed miRNAs were found between W1 and S1; 98 differentially expressed miRNAs were found between W4 and S4 (ssc-mir-146b had the largest difference and ssc-mir-215 had the highest expression level); and 22 differentially expressed miRNAs were found between W7 and S7. Sequencing miRNA results were validated using RT-qPCR. Approximately 12,819 miRNA-mRNA interactions corresponding to 4,250 target genes were predicted. The biological analyses revealed that the differentially expressed miRNAs regulated small intestinal metabolism, stressful responses, cellular and immune functions and miRNA biosynthesis in piglets. Therefore, the small intestine miRNA transcriptome was significantly different between weaning and suckling piglets; the difference varied with the number of days after weaning. six small RNA libraries from weaning piglets at 1, 4 and 7 d after weaning and from suckling piglets on the same days as the weaning piglets, respectively. For every small RNA library construction, 4 biological total RNA samples isolated from each treatment and control were separately pooled with equal contribution.
Project description:MicroRNAs (miRNAs) play important roles in intestinal diseases; however, the role of miRNAs during weaning stress is unknown. In our study, six jejunal small RNA libraries constructed from weaning piglets at 1, 4 and 7 d after weaning (libraries W1, W4 and W7, respectively) and from suckling piglets on the same days as the weaning piglets (libraries S1, S4 and S7, respectively) were sequenced using Solexa high-throughput sequencing technology. Overall, 260 known swine miRNAs and 317 novel candidate miRNA precursors were detected in the six libraries. The results revealed that 16 differentially expressed miRNAs were found between W1 and S1; 98 differentially expressed miRNAs were found between W4 and S4 (ssc-mir-146b had the largest difference and ssc-mir-215 had the highest expression level); and 22 differentially expressed miRNAs were found between W7 and S7. Sequencing miRNA results were validated using RT-qPCR. Approximately 12,819 miRNA-mRNA interactions corresponding to 4,250 target genes were predicted. The biological analyses revealed that the differentially expressed miRNAs regulated small intestinal metabolism, stressful responses, cellular and immune functions and miRNA biosynthesis in piglets. Therefore, the small intestine miRNA transcriptome was significantly different between weaning and suckling piglets; the difference varied with the number of days after weaning.
Project description:Intrauterine growth restriction (IUGR) is associated with increased relative liver weight at birth, hepatic function decline, and a higher risk for chronic liver and cardiovascular diseases in adults. Precise mechanisms of early developmental plasticity to intervene in poor fetal programming and adult disease remain largely elusive and warrant extensive research. Selecting natural piglets’ model of IUGR, using the liver as a readout and combining previous transcriptome findings, a map of cellular landscape was created to reveal a sex-dependent manner in IUGR-induced hepatic injury and its long-term functional repercussions.Here, we show data on the transcriptional profiles of 41,969 high-quality cells from normal birthweight (NBWs) and IUGR piglets (IUGRs) from hepatic tissue and demonstrated strong homology with human using human-derived liver single-cell dataset. We discovered that male liver was much more severely damaged and inflammation by IUGR than female liver at the one-week postnatal node.
Project description:Intrauterine growth restriction (IUGR) is associated with increased relative liver weight at birth, hepatic function decline, and a higher risk for chronic liver and cardiovascular diseases in adults. Precise mechanisms of early developmental plasticity to intervene in poor fetal programming and adult disease remain largely elusive and warrant extensive research. Selecting natural piglets’ model of IUGR, using the liver as a readout and combining previous transcriptome findings, a map of cellular landscape was created to reveal a sex-dependent manner in IUGR-induced hepatic injury and its long-term functional repercussions.Here, we show data on the transcriptional profiles of 41,969 high-quality cells from normal birthweight (NBWs) and IUGR piglets (IUGRs) from hepatic tissue and demonstrated strong homology with human using human-derived liver single-cell dataset. We discovered that male liver was much more severely damaged and inflammation by IUGR than female liver at the one-week postnatal node.
Project description:Regulatory Mechanisms of Atrial Remodeling of Mitral Regurgitation Pigs This study enrolled 6 pigs (age: 18 months) and divided into three groups: mitral regurgitation pigs (MR) (n = 2; 2 males sacrificed 12 months after surgery), MR pigs treated with valsartan (MRV) (n = 2; 2 males age-matched to MR sacrificed 12 months after surgery), and normal control pigs (NC) (n = 2; 2 males age-matched to MR pigs). Valsartan (3.43 mg/kg/day), a type I angiotensin II receptor blocker, was administered from one week before surgery and then daily after surgery in the MRV group. We sought to systemically elucidate critical differences in the alteration of RNA expression pattern between the atrial myocardium of pigs with and without MR, and between the atrial myocardium of MR pigs with and without valsartan using high-density oligonucleotide microarrays and functional network enrichment analysis.