Intrauterine Growth Restriction Piglets Research Articles

Lactobacillus amylovorus Promotes Lactose Utilization in Small Intestine and Enhances Intestinal Barrier Function in Intrauterine Growth Restricted Piglets

BackgroundIntrauterine growth restriction (IUGR) resulted in high mortality and many physiological defects of piglets, causing huge economic loss in the swine industry. Lactobacillus amylovorus (L. amylovorus) was identified as one of the main differential bacteria between IUGR and normal piglets. However, the effects of L. amylovorus on the growth performance and intestinal health in IUGR piglets remained unclear. ObjectivesThis study aimed to investigate the promoting effects of L. amylovorus Mafic1501, a new strain isolated from normal piglets, on the growth performance and intestinal barrier functions in IUGR piglets. MethodsNewborn mice or piglets were assigned into 3 groups: CON (normal birth weight, control), IUGR (low birth weight), and IUGR+L. amy (low birth weight), administered with sterile saline or L. amylovorus Mafic1501, respectively. Growth performance, lactose content in the digesta, intestinal lactose transporter, and barrier function parameters were profiled. IPEC-J2 cells were cultured to verify the effects of L. amylovorus Mafic1501 on lactose utilization and intestinal barrier functions. ResultsL. amylovorus Mafic1501 elevated body weight and average daily gain of IUGR mice and piglets (P < 0.05). The lactose content in the ileum was decreased, whereas gene expression of glucose transporter 2 (GLUT2) was increased by L. amylovorus Mafic1501 in IUGR piglets during suckling period (P < 0.05). Besides, L. amylovorus Mafic1501 promoted intestinal barrier functions by increasing the villus height and relative gene expressions of tight junctions (P < 0.05). L. amylovorus Mafic1501 and its culture supernatant decreased the lactose level in the medium and upregulated gene expressions of transporter GLUT2 and tight junction protein Claudin-1 of IPEC-J2 cells (P < 0.05). ConclusionL. amylovorus Mafic1501 improved the growth performance of IUGR piglets by promoting the lactose utilization in small intestine and enhancing intestinal barrier functions. Our results provided the new evidence of L. amylovorus Mafic1501 for its application in the swine industry.

Intrauterine growth restriction defined by increased brain-to-liver weight ratio affects postnatal growth and protein efficiency in pigs

Intrauterine growth restriction (IUGR) refers to impaired foetal growth during gestation, resulting in permanent stunting effects on the offspring. This study aimed to investigate the effects of IUGR on growth performance, body composition, blood metabolites, and meat quality of pigs from birth (n = 268) to slaughter (n = 93). IUGR piglets have prioritised brain development as a foetal adaptive reaction to placental insufficiency. This survival mechanism results in a higher brain-to-liver weight ratio (BrW/LW). One day (±1) after birth, computed tomography (CT) was performed on each piglet to assess their brain and liver weights. A threshold value of 0.78 (mean + SD) was chosen to divide the piglets into two categories – NORM (BrW/LW < 0.78) and IUGR (BrW/LW > 0.78). Moreover, each piglet was classified as either normal (score 1), mild IUGR (score 2), or severe IUGR (score 3) based on the head morphology. BW was recorded weekly, and average daily gain (ADG) was calculated for lactation, starter, grower, and finisher periods. Body composition was assessed after weaning (29.6 ± 0.7 d), at 20 kg (64 ± 7.2 d), 100 kg (165 ± 12.3 d), and on the carcasses using Dual-energy X-ray absorptiometry (DXA). Content and deposition rates of single nutrients, as well as energy and CP efficiency, were measured at 20 and 100 kg. Feed intake was recorded from 20 kg to slaughter. Meat quality was assessed on the carcasses. A total of 70% of the piglets assigned a score of 3 were NORM according to their BrW/LW. The IUGR category showed a lower ADG in the lactation (P < 0.01), starter (P = 0.07), and grower phases (P < 0.05) and a reduced CP efficiency in the grower–finisher period (P < 0.01) compared to the NORM group. IUGR pigs had a lower gain-to-feed ratio in the finisher period (P = 0.01) despite similar average daily feed intake, and they required more days (P < 0.01) to reach the slaughter weight. Additionally, their meat was darker (P = 0.01) than that of NORM pigs. The BrW/LW was inversely proportional to the ADG from birth to slaughter and negatively correlated with the CP deposition rate and efficiency in the grower–finisher period (P < 0.01). Furthermore, the higher the BrW/LW, the longer it took the pigs to reach the slaughter weight (P < 0.01). In conclusion, the identification of IUGR piglets based on the head morphology does not always agree with an increased BrW/LW. IUGR affects growth performance from birth to slaughter, CP efficiency in the grower–finisher period and meat quality.

Synthesis of glycine from 4-hydroxyproline in tissues of neonatal pigs with intrauterine growth restriction.

This study tested the hypothesis that the synthesis of glycine from 4-hydroxyproline (an abundant amino acid in milk and neonatal blood) was impaired in tissues of piglets with intrauterine growth restriction (IUGR), thereby contributing to a severe glycine deficiency in these compromised neonates. At 0, 7, 14, and 21 days of age, IUGR piglets were euthanized, and tissues (liver, small intestine, kidney, pancreas, stomach, skeletal muscle, and heart) were obtained for metabolic studies, as well as the determination of enzymatic activities, cell-specific localization, and expression of mRNAs for glycine-synthetic enzymes. The results indicated relatively low enzymatic activities for 4-hydroxyproline oxidase (OH-POX), proline oxidase, serine hydroxymethyltransferase, threonine dehydrogenase (TDH), alanine: glyoxylate transaminase, and 4-hydroxy-2-oxoglutarate aldolase in the kidneys and liver from 0- to 21-day-old IUGR pigs, in the pancreas of 7- to 21-day-old IUGR pigs, and in the small intestine and skeletal muscle (except TDH) of 21-day-old IUGR pigs. Accordingly, the rates of conversion of 4-hydroxyproline into glycine were relatively low in tissues of IUGR piglets. The expression of mRNAs for glycine-synthetic enzymes followed the patterns of enzymatic activities and was also low. Immunohistochemical analyses revealed the relatively low abundance of OH-POX protein in the liver, kidney, and small intestine of IUGR piglets, and the lack of OH-POX zonation in their livers. These novel results provide a metabolic basis to explain why the endogenous synthesis of glycine is insufficient for optimum growth of IUGR piglets and have important implications for improving the nutrition and health of other mammalian neonates including humans with IUGR.

Dietary Methionine Restriction Alleviates Hyperglycemia in Pigs with Intrauterine Growth Restriction by Enhancing Hepatic Protein Kinase B Signaling and Glycogen Synthesis

BackgroundIndividuals with intrauterine growth restriction (IUGR) are prone to developing type 2 diabetes mellitus (T2DM). Dietary methionine restriction (MR) improves insulin sensitivity and glucose homeostasis in individuals with normal birth weight (NBW). ObjectiveThis study investigated the effects of MR on plasma glucose concentration and hepatic and muscle glucose metabolism in pigs with IUGR. MethodsThirty female NBW and 60 same-sex spontaneous IUGR piglets (Landrace × Yorkshire) were selected. After weaning (day 21), the piglets were fed diets with adequate methionine (NBW-CON and IUGR-CON) or 30% less methionine (IUGR-MR) (n = 6). At day 180, 1 pig with a body weight near the mean of each replication was selected for biochemical analysis. ResultsThe IUGR-CON group showed 41.6%, 68.6%, and 67.1% higher plasma glucose concentration, hepatic phosphoenolpyruvate carboxykinase activity, and glucose-6-phosphatase activity, respectively, than the NBW-CON group (P < 0.05). Muscle glycogen content and glycogen synthase activity were 36.9% and 38.8% lower, respectively, in the IUGR-CON than the NBW-CON group (P < 0.05), respectively, and there was decreased hepatic and muscle protein kinase B phosphorylation in the IUGR-CON group (P < 0.05). Compared with the IUGR-CON pigs, the IUGR-MR pigs had 28.7% lower plasma glucose concentrations (P < 0.05), which were similar to those of the NBW-CON pigs (P ≥ 0.05). The hepatic glycogen content and glycogen synthase activity of the IUGR-MR pigs were 62.9% and 50.8% higher than those of the IUGR-CON pigs (P < 0.05) and 53.5% and 84.3% higher than the NBW-CON pigs (P < 0.05), respectively. The IUGR-MR pigs’ hepatic and muscle protein kinase B phosphorylation was higher than that of the IUGR-CON pigs (P < 0.05) and similar to that of the NBW-CON pigs (P ≥ 0.05). ConclusionsMR attenuates hyperglycemia in IUGR pigs by enhancing hepatic protein kinase B signaling and glycogen synthesis, implying a potential nutritional strategy to prevent type 2 diabetes mellitus in IUGR offspring.

Pituitary-Gland-Based Genes Participates in Intrauterine Growth Restriction in Piglets.

Intrauterine growth restriction (IUGR) is a major problem associated with piglet growth performance. The incidence of IUGR is widespread in Rongchang pigs. The pituitary gland is important for regulating growth and metabolism, and research has identified genes associated with growth and development. The pituitary gland of newborn piglets with normal birth weight (NBW group, n = 3) and (IUGR group, n = 3) was collected for transcriptome analysis. A total of 323 differentially expression genes (DEGs) were identified (|log2(fold-change)| > 1 and q value < 0.05), of which 223 were upregulated and 100 were downregulated. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the DEGs were mainly related to the extracellular matrix, regulation of the multicellular organismal process, tissue development and angiogenesis, which participate in the growth and immune response in IUGR piglets. Moreover, 7 DEGs including IGF2, THBS1, ITGA1, ITGA8, EPSTI1, FOSB, and UCP2 were associated with growth and immune response. Furthermore, based on the interaction network analysis of the DEGs, two genes, IGF2 and THBS1, participated in cell proliferation, embryonic development and angiogenesis. IGF2 and THBS1 were also the main genes participating in the IUGR. This study identified the core genes involved in IUGR in piglets and provided a reference for exploring the effect of the pituitary gland on piglet growth.

Altered Liver Metabolism, Mitochondrial Function, Oxidative Status, and Inflammatory Response in Intrauterine Growth Restriction Piglets with Different Growth Patterns before Weaning.

Frequent occurrence of intrauterine growth restriction (IUGR) causes huge economic losses in the pig industry. Accelerated catch-up growth (CUG) in the early stage of life could restore multiple adverse outcomes of IUGR offspring; however, there is little knowledge about this beneficial phenomenon. We previously found that nutrient absorption related to intestinal function was globally promoted in CUG-IUGR piglets before weaning, which might be the dominant reason for CUG, but what this alteration could lead to in subsequent liver metabolism is still unknown. Firstly, a Normal, CUG, and non-catch-up growth (NCUG) piglet model before weaning was established by dividing eighty litters of newborn piglets into normal birth weight (NBW) and IUGR groups according to birth weight, and those piglets with IUGR but above-average weanling body weight were considered CUG, and the piglets with IUGR still below average body weight were considered NCUG at weaning day (d 26). Liver samples were collected and then systematically compared in glycolipid metabolism, mitochondrial function, antioxidant status, and inflammatory status among these three different growth models. Enhanced hepatic uptake of fatty acids, diminished de novo synthesis of fatty acids, and increased oxidation of fatty acids were observed in CUG livers compared to Normal and NCUG. In contrast, the NCUG liver showed enhanced glucose uptake and gluconeogenesis compared to Normal and CUG. We also observed deteriorating hepatic vacuolation in NCUG piglets, while increasing hepatic lipid deposition in CUG piglets. Besides, the expression of genes related to mitochondrial energy metabolism and biogenesis was reduced in CUG piglets and the phosphorylation level of AMPK was significantly higher compared to Normal (p < 0.05). Moreover, NCUG liver showed decreased T-AOC (p < 0.01) and GSH-PX (p < 0.05), increased MDA concentrations (p < 0.01), upregulated phosphorylation levels of ERK and NF-κB (p < 0.05), and elevated pro-inflammatory factors IL-1β, IL-6 and TNF-α (p < 0.05) compared to Normal. Furthermore, correlation analysis revealed a significant positive correlation between glucose metabolism and inflammatory factors, while a negative correlation between mitochondrial function-related genes and fatty acid transport. NGUG piglets showed simultaneous enhancement of glucose uptake and gluconeogenesis, as well as reduced antioxidant capacity and increased inflammatory status, whereas CUG comes at the expense of impaired hepatic mitochondrial function and pathological fat accumulation.

Integrative Analysis of Liver Metabolomics and Transcriptomics Reveals Oxidative Stress in Piglets with Intrauterine Growth Restriction.

Simple SummaryAlthough the correlation between oxidative stress and liver metabolic dysfunction has been established in piglets with intrauterine growth restriction, detailed information concerning the molecular mechanisms that facilitate this relationship remains limited. In the present study, metabolomic and transcriptomic techniques were used to investigate differences in gene expression and metabolites in the liver of piglets in intrauterine growth restriction and normal birth weight groups to systematically analyze the potential mechanism of metabolic characteristics induced by oxidative stress in the liver of intrauterine growth restriction piglets. Our results revealed that the intrauterine growth restriction piglets were involved in a variety of metabolic abnormalities, including mitochondrial dysfunction, imbalance of fatty acid composition, disruption to sources of one-carbon unit supply, and abnormal galactose conversion, which may be responsible for oxidative stress in the liver.The correlation between oxidative stress and liver metabolic dysfunction in piglets with intrauterine growth restriction (IUGR) remains limited. Therefore, the objective of the present study was to investigate potential mechanisms of metabolic characteristics induced by oxidative stress in the livers of IUGR piglets using metabolomic and transcriptomic analysis. Analysis of the phenotypic characteristics showed that the liver weight of the intrauterine growth restriction piglets was significantly lower than that of normal birth weight piglets. Intrauterine growth restriction piglets exhibited disordered hepatic cord arrangement and vacuolization as well as excessive lipid accumulation in hepatocytes. In addition, the activities of antioxidant enzymes were significantly decreased in the liver of the intrauterine growth restriction piglets, whereas the level of the lipid peroxidation marker MDA was significantly increased. Finally, our findings revealed that intrauterine growth restriction piglets were involved in a variety of metabolic abnormalities, including mitochondrial dysfunction, imbalance of fatty acid composition, disruption to sources of one-carbon unit supply, and abnormal galactose conversion, which may be responsible for oxidative stress in the liver. In summary, these data provided a detailed theoretical reference for revealing the hepatic metabolic characteristics of intrauterine growth restriction piglets.

Metabolome, microbiome, and gene expression alterations in the colon of newborn piglets with intrauterine growth restriction.

Newborn animals with intrauterine growth restriction (IUGR) are characterized by impaired intestinal structure and function; however, their intestinal microbiota and metabolome profiles have not been fully identified. The present study investigated the differences in colonic microbiota, metabolomics, and barrier function-related gene expression profiles between the IUGR and normal birth weight (NBW) piglets at 7, 21, and 28 days of age. Forty-eight piglets (24 NBW and 24 IUGR) from 24 litters were assigned to assess the differences in colonic microbiota, metabolomics, and gene expression between IUGR and NBW piglets. Compared with the NBW piglets, IUGR piglets showed decreased Shannon index and increased Simpson index at 7 days of age and Chao1 index at 21 days of age (p < 0.05). The IUGR piglets had lower abundances of Firmicutes, Subdoligranulum, Ruminococcaceae_UCG-002, and Ruminococcaceae_UCG-003 at 7 days of age, and Bacteroidetes, Phascolarctobacterium, and Ruminococcaceae_UCG-005 at 21 days of age, when compared with the NBW piglets (p < 0.05). Metabolomics analysis showed significant changes in 147 metabolites mainly involved in organic acids and their derivatives in the colon. Six differential metabolic pathways were significantly enriched, including purine metabolism, amino sugar/nucleotide sugar metabolism, ubiquinone/other terpenoid-quinone biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, phenylalanine metabolism, and histidine metabolism. Spearman’s correlation analysis further demonstrated significant correlations between colonic microbiota and metabolites. In addition, colonic isobutyrate at 7 days of age, isovalerate and total short-chain fatty acids (SCFAs) at 21 days of age, and acetate, propionate, butyrate, and total SCFAs levels at 28 days of age were lower and isovalerate was higher at 28 days of age in the IUGR piglets than in the NBW piglets (p < 0.05). Furthermore, the mRNA expression of zonula occludens (ZO)-1 at 7 days of age, ZO-1, occludin, and interleukin (IL)-4 at 21 days of age were down-regulated in the IUGR piglets, whereas tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) at 28 days of age were up-regulated, when compared with the NBW piglets (p < 0.05). The findings suggest that the IUGR pigs present abnormal microbiota and nutrient metabolism in the colon, which may further affect the intestine barrier function by regulating gene expressions.

L-leucine supplementation reduces growth performance accompanied by changed profiles of plasma amino acids and expression of jejunal amino acid transporters in breast-fed intra-uterine growth-retarded piglets.

Previously, we provided an evidence that L-leucine supplementation facilitates growth performance in suckling piglets with normal birth weight. However, it remains hitherto obscure weather breast-fed piglets displaying intrauterine growth restriction (IUGR) show a similar effect in response to L-leucine provision. In this study, seven-day-old sow-reared IUGR piglets were orally administrated with L-leucine (0, 0.7 1.4, 2.1 g/kg BW) twice daily for two weeks. Increasing leucine levels hampered the growth performance of suckling IUGR piglets. The average daily gain of IUGR piglets was significantly reduced in 1.4 g/kg BW and 2.1 g/kg BW L-leucine supplementation groups (P < 0.05). Except for ornithine and glutamine, the plasma concentrations of other amino acids were abated as L-leucine levels increased (P < 0.05). Leucine supplementation led to reduction in the levels of urea, blood ammonia, blood glucose, triglyceride, and total cholesterol, as well as an elevation in the level of low density lipoprotein cholesterol in suckling IUGR piglets (P < 0.05). In addition, 1.4g/kg BW of L-leucine enhanced the mRNA expression of ATB 0,+ , whereas decreased the mRNA abundances of CAT1, y+LAT1, ASCT2 and b 0,+ AT in the jejunum (P < 0.05). Concomitantly, the jejunum of IUGR piglets in L-leucine group contains more ATB0,+ and less SNAT2 protein than in the control (P < 0.05). Collectively, L-leucine supplementation impairs growth performance in breast-fed IUGR piglets, which may be associated with depressed nutritional conditions and alterations in the uptake of amino acids and the expression of amino acid transporters in the small intestine.

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.

Treatment of immune dysfunction in intrauterine growth restriction piglets via supplementation with dimethylglycine sodium salt during the suckling period.

This study aimed to investigate the mechanism of small intestinal immune dysfunction in intrauterine growth restriction (IUGR) newborn piglets and relieve this dysfunction via dimethylglycine sodium salt (DMG-Na) supplementation during the suckling period. Thirty sows (Duroc × [Landrace × Yorkshire]) were selected, and 1 male newborn piglet with normal birth weight (NBW) and 1 male newborn piglet with IUGR were obtained from each sow. Among them, 10 NBW and 10 IUGR newborns were euthanized without suckling. The other 20 NBW newborns were allocated to the group named NCON, which means NBW newborns fed a basic milk diet (BMD) (n = 10), and the group named ND, which means NBW newborns fed BMD supplemented with 0.1% DMG-Na (n = 10); the other 20 IUGR newborns were assigned to the group named ICON, which means IUGR newborns fed BMD (n = 10), and the group named ID, which means IUGR newborns fed BMD supplemented with 0.1% DMG-Na (n = 10). The newborns were fed BMD from 7 to 21 d of age and euthanized at 21 d of age to collect serum and small intestinal samples. The growth performance, small intestinal histological morphology and sub-organelle ultrastructure, serum immunoglobulin, small intestinal digestive enzyme activity, inflammatory cytokine level, and jejunum mRNA and protein expression of the toll-like receptor 4 (TLR4)/nucleotide-binding oligomerization domain protein (NOD)/nuclear factor-κB (NF-κB) network deteriorated in the ICON group compared to that in the NCON group. The small intestinal histological morphology and sub-organelle ultrastructure, serum immunoglobulin, small intestinal digestive enzyme activity, and inflammatory cytokine level improved (P < 0.05) in the ID group compared to those in the ICON group. The jejunum mRNA and protein expression of the TLR4/NOD/NF-κB network improved (P < 0.05) in the ID group compared to that in the ICON group. In conclusion, the activity of the TLR4/NOD/NF-κB pathway was inhibited in the IUGR newborns, which in turn led to their jejunum immune dysfunction and reduced their performance. By ingesting DMG-Na, the IUGR newborns activated the TLR4/NOD/NF-κB pathway, thereby improving their unfavorable body state during the suckling period.

Preweaning performance in intrauterine growth-restricted piglets: Characteristics and interventions.

Intrauterine growth restriction (IUGR) is frequently observed in pig production, especially when using highly prolific sows. IUGR piglets are born with low body weight and shape indicative of differences in organ growth. Insufficient uteroplacental nutrient transfer to the fetuses is the leading cause of growth restriction in the pig. Supplementing the sow's gestation diet with arginine and/or glutamine improves placenta growth and functionality and consequently is able to reduce IUGR incidence. IUGR piglets are at higher risk of dying preweaning and face higher morbidity than their normal-weight littermates. A high level of surveillance during farrowing and individual nutrient supplementation can reduce the mortality rates. Still, these do not reverse the long-term consequences of IUGR, which are induced by persistent structural deficits in different organs. Dietary interventions peri-weaning can optimize performance but these are less effective in combating the metabolic changes that occurred in IUGR, which affect reproductive performance later in life. IUGR piglets share many similarities with IUGR infants, such as a poorer outcome of males. Using the IUGR piglet as an animal model to further explore the structural and molecular basis of the long-term consequences of IUGR and the potential sex bias could aid in fully understanding the impact of prenatal undernutrition and finding solutions for both species and sexes.

Intrauterine Growth-Restricted Piglets Are Predisposed to Develop Metabolic Disorders in Adulthood When Fed With Parenteral Nutrition in the Neonatal Period

ObjectivesTotal parenteral nutrition (TPN) is lifesaving yet non-normal nutrition regimen during the neonatal period. However, studies have shown that TPN feeding early in life can permanently alter metabolism at later ages. Moreover, intrauterine growth restricted (IUGR) neonates also have a higher risk of developing metabolic diseases (such as obesity and dyslipidemia) in later life. Because a substantial proportion of IUGR neonates receive TPN in early life, we wondered if the metabolic effects of feeding TPN early in life would exacerbate these effects of IUGR? We hypothesized that feeding TPN to IUGR neonates would aggravate the risk of developing obesity and dyslipidemia in adulthood.MethodsSixteen normal weight female piglets (7 d old) were randomized to sow-fed (SF) or early TPN (TPN-CON); 8 (IUGR or runt) piglets were fed TPN as a third group (TPN-IUGR). After 2 weeks of TPN or suckling, all pigs were fed a normal grower diet for 8 mo. At 8 mo, catheters were implanted and in vivo metabolic tests were conducted.ResultsTPN-IUGR pigs demonstrated catch-up growth by 4 mo, and body weights were not different among groups at 8 mo. The metabolic effects of feeding TPN persisted into adulthood, as indicated by higher postprandial plasma triglycerides (TG) and fasting plasma non-esterified fatty acids (NEFA), compared to SF (P < 0.05). IUGR exacerbated TPN-induced risk for diseases by worsening obesity outcomes with greater subcutaneous fat deposition (P < 0.05) and greater ectopic TG deposition in the liver (P < 0.05) and muscle (P < 0.05). Furthermore, IUGR led to dyslipidemia as indicated by higher cholesterol in fasted plasma LDL (P < 0.05), slower postprandial TG clearance (P < 0.05), higher fasting plasma NEFA (P < 0.001) and higher plasma dimethylglycine (P < 0.05), compared to the TPN-CON. IUGR pigs had greater VLDL secretion, as suggested by higher microsomal transfer protein mRNA (P < 0.05). Early TPN programmed reduced lipogenesis, as indicated by lower fatty acid synthase mRNA (P < 0.05), compared to SF.ConclusionsCollectively, these findings conclude that although TPN is a lifesaving measure, feeding TPN to IUGR neonates has long-term metabolic consequences predisposing them to develop metabolic disorders in adulthood.Funding SourcesCanadian Institutes of Health Research.

P96 Nutritional effects of bovine or vegetable oils on plasma IGF-1 levels of intrauterine growth restricted piglets compared to normal piglets

P96 Nutritional effects of bovine or vegetable oils on plasma IGF-1 levels of intrauterine growth restricted piglets compared to normal piglets

Curcumin and Intestinal Oxidative Stress of Pigs With Intrauterine Growth Retardation: A Review.

Intrauterine growth restriction (IUGR) refers to the slow growth and development of a mammalian embryo/fetus or fetal organs during pregnancy, which is popular in swine production and causes considerable economic losses. Nutritional strategies have been reported to improve the health status and growth performance of IUGR piglets, among which dietary curcumin supplementation is an efficient alternative. Curcumin is a natural lipophilic polyphenol derived from the rhizome of Curcuma longa with many biological activities. It has been demonstrated that curcumin promotes intestinal development and alleviates intestinal oxidative damage. However, due to its low bioavailability caused by poor solubility, chemical instability, and rapid degradation, the application of curcumin in animal production is rare. In this manuscript, the structural-activity relationship to enhance the bioavailability, and the nutritional effects of curcumin on intestinal health from the aspect of protecting piglets from IUGR associated intestinal oxidative damage were summarized to provide new insight into the application of curcumin in animal production.

Leucine alters blood parameters and regulates hepatic protein synthesis via mammalian/mechanistic target of rapamycin activation in intrauterine growth-restricted piglets.

Neonatal piglets often suffer low birth weights and poor growth performance accompanied by the disruption of protein metabolism, when intrauterine growth restriction (IUGR) takes place during pregnancy, leading to a higher mortality and bigger economic loss than expected. Leucine has been proposed to function as a nutritional signal-regulating protein synthesis in numerous studies. The aim of this study was to determine the effect of dietary leucine supplementation on the blood parameters and hepatic protein metabolism in IUGR piglets. Weaned piglets were assigned to one of four treatments in a 2 × 2 factorial arrangement: 1) piglets fed a basal diet with normal birth weight, 2) piglets fed a basal diet plus 0.35% l-leucine with normal birth weight, 3) IUGR piglets fed a basal diet with low birth weight, and 4) IUGR piglets fed a basal diet plus 0.35% l-leucine with low birth weight. The results showed that IUGR decreased serum aspartate aminotransferase and alkaline phosphatase activities and increased serum cortisol and prostaglandin E2 levels at 35 d of age (P < 0.05), suggesting the occurrence of liver dysfunction and stress response. Leucine supplementation increased serum alkaline phosphatase activity and decreased serum cortisol levels at 35 d of age (P < 0.05). IUGR decreased the lysozyme activity and complement 3 level in serum (P < 0.05), which were prevented by dietary leucine supplementation. IUGR piglets showed increased hepatic DNA contents while showing a reduced RNA/DNA ratio (P < 0.05). Piglets supplied with leucine had decreased RNA/DNA ratio in the liver (P < 0.05). Leucine supplementation stimulated hepatic protein anabolism through upregulating protein synthesis-related genes expression and activating the phosphorylation of mammalian/mechanistic target of rapamycin (mTOR) (P < 0.05). Moreover, IUGR inhibited the mRNA expression of hepatic protein degradation-related genes, indicating a compensatory mechanism for the metabolic response. Dietary leucine supplementation attenuated the suppression of the protein catabolism induced by IUGR in the liver. These results demonstrate that dietary leucine supplementation could alter the blood parameters and alleviated the disrupted protein metabolism induced by IUGR via enhanced mTOR phosphorylation to promote protein synthesis in weaned piglets.

Associations between testicular development and fetal size in the pig

BackgroundImpaired reproductive performance is the largest contributing factor for the removal of boars from commercial systems. Intrauterine growth restricted piglets represent 25% of the total number of piglets born and have impaired reproductive performance. This study aimed to improve the understanding of temporal changes in testicular gene expression during testes development in fetuses of different size. The lightest and closest to mean litter weight (CTMLW) male Large White × Landrace littermates were collected at gestational days (GD) 45, 60 and 90 (n = 5–6 litters/GD).ResultsTestes weight and testes weight as a percentage of fetal weight were not associated with fetal size at GD60 or 90. Fetal plasma testosterone was not associated with fetal size at GD90. There was no association between fetal size and seminiferous tubule area and number, number of germ or Sertoli cells per tubule. The lightest fetuses tended to have wider seminiferous tubules compared to the CTMLW fetuses at GD90 (P = 0.077). The testicular expression of KI67 (P ≤ 0.01) and BAX:BCL2 ratio (P = 0.058) mRNAs decreased as gestation progressed. Greater SPP1 mRNA expression was observed at GD60 when compared with GD45 and 90 (P ≤ 0.05). Lower expression of DMRT1 and SPP1 (P < 0.01) mRNAs was observed in testes associated with the lightest fetuses compared to the CTMLW fetuses at GD90.ConclusionsThese findings provide novel insights into the expression profiles of genes associated with testicular development and function. Further, these data suggest that programming of reproductive potential in IUGR boars occurs late in gestation, providing a platform for further mechanistic investigation.

Brain lipidomics and neurodevelopmental outcomes in intrauterine growth restricted piglets fed dairy or vegetable fat diets

Breast milk has neurodevelopmental advantages compared to infant formula, especially in low-birth-weight infants, which may in part relate to the fat source. This study compared neurodevelopmental outcomes in three-day-old normal birth weight (NBW) and intrauterine growth restricted (IUGR) piglets fed a formula diet with either vegetable oil (VEG) or bovine milk fat sources (MILK) for three weeks in a 2 × 2 factorial design. Behavioural tests, lipidomics, MRI and RNA sequencing analyses of plasma and brain tissue were conducted. The absolute levels of 82% and 11% of lipid molecules were different between dietary groups in plasma and hippocampus, respectively. Of the lipid molecules with differential abundance in the hippocampus, the majority were upregulated in MILK versus VEG, and they mainly belonged to the group of glycerophospholipids. Lower absolute brain weights, absolute grey and white matter volumes and behaviour and motor function scores, and higher relative total brain weights were present in IUGR compared to NBW with minor influence of diet. Cognitive function and cerebellar gene expression profiles were similar for dietary and weight groups, and overall only minor interactive effects between diet and birth weight were observed. Overall, we show that the dietary fat source influences the plasma and to a lesser degree the hippocampal lipidome and is unable to improve on IUGR-induced brain structural and functional impairments.

L-Arginine Supplementation for Nulliparous Sows during the Last Third of Gestation.

Simple SummaryNutrition of gestating sows plays an important role in the uteroplacental efficiency, muscle development, birth weight and viability of the piglets. This is especially important for nulliparous sows, since the reproductive performance of nulliparous sows is lower compared to multiparous ones. Previous studies have shown that arginine enhances angiogenesis and placental growth, being beneficial to fetus growth. Because during its formation process skeletal muscle tissue compete for nutrients with other organs also in formation during the intrauterine development, the increase of nutrient flow by enhancing angiogenesis may benefit the skeletal muscle formation during the fetal stage. In this sense, arginine supplementation for sows seems to be a promising nutritional strategy to maximize myogenesis and muscle development of piglets. In the present study, piglets born from sows fed diet with 1.0% L-arginine (ARG) had greater mRNA expression of the gene encoding myoblast determination protein (MYOD) and myogenin (MYOG) compared to the piglets born from sows at the control group. The mRNA expression of IGF-2 gene tended to be greater in piglets born from ARG sows compared to those born from control sows. Despite differences in gene expression, no differences in the histomorphometric variables of skeletal muscle were observed between piglets from arginine-supplemented and control sows. In conclusion, supplementation of 1.0% L-arginine for nulliparous sows from 85 to 114 days of gestation increased mRNA expression of the myogenic regulatory factors MYOD and MYOG and IGF-2 in skeletal muscle of piglets.We evaluated the effects of L-arginine supplementation during the last third of gestation on molecular mechanisms related to skeletal muscle development of piglets and litter traits at birth. Twenty-three nulliparous sows averaging 205.37 ± 11.50 kg of body weight were randomly assigned to the following experimental treatments: control (CON), where pregnant sows were fed diets to meet their nutritional requirements; arginine (ARG), where sows where fed CON + 1.0% L-arginine. Skeletal muscle from piglets born from sows from ARG group had greater mRNA expression of MYOD (p = 0.043) and MYOG (p ≤ 0.01), and tended to present greater mRNA expression (p = 0.06) of IGF-2 gene compared to those born from CON sows. However, there were no differences (p > 0.05) in the histomorphometric variables of fetuses’ skeletal muscle. The total weight of born piglets, total weight of born alive piglets, piglet weight at birth, coefficient of variation of birth weight, and the incidence of intrauterine growth restriction (IUGR) piglets did not differ between groups. No stillborn piglets (p < 0.01) were verified in the ARG sows compared to CON group. The blood levels of estradiol (p = 0.035) and urea (p = 0.03) were higher in ARG sows compared to those from the CON group. In summary, our data show that arginine supplementation of nulliparous sows at late gestation enhance mRNA expression of key myogenic regulatory factors, which likely contribute to improve animal growth rates in later stages of development.

Inclusion of Soluble Fiber During Gestation Regulates Gut Microbiota, Improves Bile Acid Homeostasis, and Enhances the Reproductive Performance of Sows

Interaction between the dietary fiber and the gut microbes can regulate host bile acid metabolism. This study sought to explore the effects of guar gum combined with pregelatinized waxy maize starch (GCW) in a gestation diet on reproductive performance, gut microbiota composition, and bile acid homeostasis of sows. A total of 61 large white sows were randomly grouped into the control (n = 33) and 2% GCW (n = 28) groups during gestation. GCW diet increased birth-weight of piglets, and decreased the percentage of intrauterine growth restriction (IUGR) piglets. In addition, dietary GCW reduced gut microbial diversity and modulated gut microbial composition in sows on day 109 of gestation. The relative abundance of bile salt hydrolase (BSH) gene-encoding bacteria, Lactobacillus and Bacteroides decreased after GCW administration, whereas no significant difference was observed in the fecal level of total glycine-conjugated and taurine-conjugated bile acids between the two groups. Dietary GCW increased the relative abundance of Ruminococcaceae (one of few taxa comprising 7α-dehydroxylating bacteria), which was associated with elevated fecal deoxycholic acid (DCA) in the GCW group. GCW administration lowered the concentrations of plasma total bile acid (TBA) and 7α-hydroxy-4-cholesten-3-one (C4) (reflecting lower hepatic bile acid synthesis) at day 90 and day 109 of gestation compared with the control diet. Furthermore, the levels of plasma glycoursodeoxycholic acid (GUDCA), tauroursodeoxycholic acid (TUDCA) and glycohyocholic acid (GHCA) were lower in the GCW group compared with the control group. Spearman correlation analysis showed alterations in the composition of the gut microbiota by GCW treatment was associated with improved bile acid homeostasis and reproductive performance of sows. In conclusion, GCW-induced improves bile acid homeostasis during gestation which may enhance reproductive performance of sows.