Intrauterine Growth Restriction Pigs Research Articles

Dietary supplementation with dihydroartemisinin improves intestinal barrier function in weaned piglets with intrauterine growth retardation by modulating the gut microbiota.

The aim of this study was to investigate whether dietary dihydroartemisinin (DHA) supplementation could improve the intestinal barrier function and microbiota composition in intrauterine growth restriction (IUGR) weaned piglets. Twelve normal birth weight (NBW) piglets and 24 IUGR piglets at 21 days of age were divided into 3 groups, which were fed a basal diet (NBW-CON and IUCR-CON groups) and an 80mg/kg DHA diet (IUGR-DHA group). At 49 days of age, 8 piglets of each group with similar body weights within groups were slaughtered, and serum and small intestine samples were collected. The results showed that IUGR piglets reduced growth performance, impaired the markers of intestinal permeability, induced intestinal inflammation, decreased intestinal immunity and disturbed the intestinal microflora. Dietary DHA supplementation increased average daily gain, average daily feed intake and body weight at 49 days of age in IUGR weaned piglets (P < 0.05). DHA treatment decreased serum diamine oxidase activity and increased the numbers of intestinal goblet cells and intraepithelial lymphocytes, concentrations of jejunal mucin-2 and ileal trefoil factor 3, and intestinal secretory immunoglobin A and immunoglobin G (IgG) concentrations of IUGR piglets (P < 0.05). Diet supplemented with DHA also up-regulated mRNA abundances of jejunal IgG, cluster of differentiation 8 (CD8), major histocompatibility complex-I (MHC-I) and interleukin 6 (IL-6) and ileal IgG, Fc receptor for IgG (FcRn), cluster of differentiation 8 (CD4), CD8, MHC-I, IL-6 and tumor necrosis factor α (TNF-α), and enhanced mRNA abundance and protein expression of intestinal occludin and ileal claudin-1 in IUGR piglets (P < 0.05). In addition, DHA supplementation in the diet improved the microbial diversity of the small intestine of IUGR piglets and significantly increased the relative abundance of Actinobacteriota, Streptococcus, Blautia and Streptococcus in the jejunum, and Clostridium sensu_ stricto_in the ileum (P < 0.05). The intestinal microbiota was correlated with the mRNA abundance of tight junction proteins and inflammatory response related genes. These data suggested that DHA could improve the markers of intestinal barrier function in IUGR weaned piglets by modulating gut microbiota. DHA may be a novel nutritional candidate for preventing intestinal dysfunction in IUGR pigs.

Dietary glycine supplementation activates mTOR signaling pathway in tissues of pigs with intrauterine growth restriction.

The mechanistic target of rapamycin (mTOR) cell signaling pathway serves as the central mechanism for the regulation of tissue protein synthesis and growth. We recently reported that supplementing 1% glycine to corn- and soybean meal-based diets enhanced growth performance between weaning and market weights in pigs with intrauterine growth restriction (IUGR). Results of recent studies have revealed an important role for glycine in activating mTOR and protein synthesis in C2C12 muscle cells. Therefore, the present study tested the hypothesis that dietary glycine supplementation enhanced the mTOR cell signaling pathway in skeletal muscle and other tissues of IUGR pigs. At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to one of two groups: supplementation with either 1% glycine or 1.19% L-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Tissues were obtained from the pigs within 1wk after the feeding trial ended at 188 d of age to determine the abundances of total and phosphorylated forms of mTOR and its two major downstream proteins: eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and ribosomal protein S6 kinase-1 (p70S6K). Results showed that IUGR decreased (P < 0.05) the abundances of both total and phosphorylated mTOR, 4EBP1, and p70S6K in the gastrocnemius muscle and jejunum. In the longissimus lumborum muscle of IUGR pigs, the abundances of total mTOR did not differ (P > 0.05) but those for phosphorylated mTOR and both total and phosphorylated 4EBP1 and p70S6K were down-regulated (P < 0.05), when compared to NBW pigs. These adverse effects of IUGR in the gastrocnemius muscle, longissimus lumborum muscle, and jejunum were prevented (P < 0.05) by dietary glycine supplementation. Interestingly, the abundances of total or phosphorylated mTOR, 4EBP1, and p70S6K in liver were not affected (P > 0.05) by IUGR or glycine supplementation. Collectively, our findings indicate that IUGR impaired the mTOR cell signaling pathway in tissues of pigs and that adequate glycine intake was crucial for maintaining active mTOR-dependent protein synthesis for the growth and development of skeletal muscle.

Intrauterine Growth Restriction Affects Colonic Barrier Function via Regulating the Nrf2/Keap1 and TLR4-NF-κB/ERK Pathways and Altering Colonic Microbiome and Metabolome Homeostasis in Growing-Finishing Pigs.

Intrauterine growth restriction (IUGR) pigs are characterized by long-term growth failure, metabolic disorders, and intestinal microbiota imbalance. The characteristics of the negative effects of IUGR at different growth stages of pigs are still unclear. Therefore, this study explored through multi-omics analyses whether the IUGR damages the intestinal barrier function and alters the colonization and metabolic profiles of the colonic microbiota in growing-finishing pigs. Seventy-two piglets (36 IUGR and 36 NBW) were allocated for this trial to analyze physiological and plasma biochemical parameters, as well as oxidative damage and inflammatory response in the colon. Moreover, the colonic microbiota communities and metabolome were examined using 16s rRNA sequencing and metabolomics technologies to reveal the intestinal characteristics of IUGR pigs at different growth stages (25, 50, and 100 kg). IUGR altered the concentrations of plasma glucose, total protein, triglycerides, and cholesterol. Colonic tight junction proteins were markedly inhibited by IUGR. IUGR decreased plasma T-AOC, SOD, and GSH levels and colonic SOD-1, SOD-2, and GPX-4 expressions by restraining the Nrf2/Keap1 signaling pathway. Moreover, IUGR increased colonic IL-1β and TNF-α levels while reducing IL-10, possibly through activating the TLR4-NF-κB/ERK pathway. Notably, IUGR pigs had lower colonic Streptococcus abundance and Firmicutes-to-Bacteroidetes ratio at the 25 kg BW stage while having higher Firmicutes abundance at the 100 kg BW stage; moreover, IUGR pigs had lower SCFA concentrations. Metabolomics analysis showed that IUGR increased colonic lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds concentrations and enriched three differential metabolic pathways, including linoleic acid, sphingolipid, and purine metabolisms throughout the trial. Collectively, IUGR altered the nutrient metabolism, redox status, and colonic microbiota community and metabolite profiles of pigs and continued to disrupt colonic barrier function by reducing antioxidant capacity via the Nrf2/Keap1 pathway and activating inflammation via the TLR4-NF-κB/ERK pathway during the growing-finishing stage. Moreover, colonic Firmicutes and Streptococcus could be potential regulatory targets for modulating the metabolism and health of IUGR pigs.

Dietary glycine supplementation enhances glutathione availability in tissues of pigs with intrauterine growth restriction.

This study tested the hypothesis that dietary supplementation with glycine enhances the synthesis and concentrations of glutathione (GSH, a major antioxidant) in tissues of pigs with intrauterine growth restriction (IUGR). At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to one of two groups, representing supplementation with 1% glycine or 1.19% l-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Blood and other tissues were obtained from the pigs within 1wk after the feeding trial ended at 188 d of age to determine GSH, oxidized GSH (GSSG), and activities of GSH-metabolic enzymes. Results indicated that concentrations of GSH + GSSG or GSH in plasma, liver, and jejunum (P < 0.001) and concentrations of GSH in longissimus lumborum and gastrocnemius muscles (P < 0.05) were lower in IUGR pigs than in NBW pigs. In contrast, IUGR increased GSSG/GSH ratios (an indicator of oxidative stress) in plasma (P < 0.001), jejunum (P < 0.001), both muscles (P < 0.05), and pancreas (P = 0.001), while decreasing activities of γ-glutamylcysteine synthetase and GSH synthetase in liver (P < 0.001) and jejunum (P < 0.01); and GSH reductase in jejunum (P < 0.01), longissimus lumborum muscle (P < 0.01), gastrocnemius muscle (P < 0.05), and pancreas (P < 0.01). In addition, IUGR pigs had greater (P < 0.001) concentrations of thiobarbituric acid reactive substances (TBARS; an indicator of lipid peroxidation) in plasma, jejunum, muscles, and pancreas than NBW pigs. Compared with isonitrogenous controls, dietary glycine supplementation increased concentrations of GSH plus GSSG and GSH in plasma (P < 0.01), liver (P < 0.001), jejunum (P < 0.001), longissimus lumborum muscle (P = 0.001), and gastrocnemius muscle (P < 0.05); activities of GSH-synthetic enzymes in liver (P < 0.01) and jejunum (P < 0.05), while reducing GSSG/GSH ratios in plasma (P < 0.001), jejunum (P < 0.001), longissimus lumborum muscle (P < 0.001), gastrocnemius muscle (P = 0.01), pancreas (P < 0.05), and kidneys (P < 0.01). Concentrations of GSH plus GSSG, GSH, and GSSG/GSH ratios in kidneys were not affected (P > 0.05) by IUGR. Furthermore, glycine supplementation reduced (P < 0.001) TBARS concentrations in plasma, jejunum, muscles, and pancreas. Collectively, IUGR reduced GSH availability and induced oxidative stress in pig tissues, and these abnormalities were prevented by dietary glycine supplementation in a tissue-specific manner.

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.

TRNA-derived small RNA dataset in multiple organs of intrauterine growth-restricted pig

Intrauterine growth restriction (IUGR) impairs neonatal weight and causes multiple organ dysplasia. IUGR not only threatens human health but is also a significant constraint to the development of animal husbandry. However, the molecular mechanism underlying IUGR remains to be further elucidated. tRNA-derived small RNA (tsRNAs) is a regulative non-coding RNA, which has recently been reported to correlate with the onset and progression of several diseases. In this study, we investigated the tsRNAs expression profiles of IUGR pigs. A tsRNAs dataset for multiple organs in normal and IUGR pigs was generated, including muscle, liver, spleen and intestine. We further analyzed the characteristics of tsRNAs in different organs of pigs, and KEGG pathway analysis was performed to investigate possible pathways involved. This dataset will provide valuable information for further exploring the molecular mechanism of IUGR formation.

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.

Characteristics of microRNAs in Skeletal Muscle of Intrauterine Growth-Restricted Pigs.

microRNAs are a class of small RNAs that have been extensively studied, which are involved in many biological processes and disease occurrence. The incidence of intrauterine growth restriction is higher in mammals, especially multiparous mammals. In this study, we found that the weight of the longissimus dorsi of intrauterine growth-restricted pigs was significantly lower than that of normal pigs. Then, intrauterine growth-restricted pig longissimus dorsi were used to characterize miRNA expression profiles by RNA sequencing. A total of 333 miRNAs were identified, of which 26 were differentially expressed. Functional enrichment analysis showed that these differentially expressed miRNAs regulate the expression of their target genes (such as PIK3R1, CCND2, AKT3, and MAP3K7), and these target genes play an important role in the proliferation and differentiation of skeletal muscle through signaling pathways such as the PI3K-Akt, MAPK, and FoxO signaling pathways. Furthermore, miRNA-451 was significantly upregulated in IUGR pig skeletal muscle. Overexpression of miR-451 in C2C12 cells significantly promoted the expression of Mb, Myod, Myog, Myh1, and Myh7, suggesting that miR-451 may be involved in the regulation of the myoblastic differentiation of C2C12 cells. Our results reveal the role of miRNA-451 in regulating myogenic differentiation of skeletal muscle in pigs with intrauterine growth restriction.

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.

Dietary glycine supplementation enhances postweaning growth and meat quality of pigs with intrauterine growth restriction.

Pigs with intrauterine growth restriction (IUGR) have suboptimum growth performance and impaired synthesis of glycine (the most abundant amino acid in the body). Conventional corn- and soybean meal-based diets for postweaning pigs contain relatively low amounts of glycine and may not provide sufficient glycine to meet requirements for IUGR pigs. This hypothesis was tested using 52 IUGR pigs and 52 litter mates with normal birth weights (NBW). At weaning (21 d of age), IUGR or NBW pigs were assigned randomly to one of two nutritional groups: supplementation of a corn-soybean meal-based diet with either 1% glycine plus 0.19% cornstarch or 1.19% L-alanine (isonitrogenous control). Feed consumption and body weight (BW) of pigs were recorded daily and every 2 or 4 wks, respectively. All pigs had free access to their respective diets and clean drinking water. Within 1 wk after the feeding trial ended at 188 d of age, blood and other tissue samples were obtained from pigs to determine concentrations of amino acids and meat quality. Neither IUGR nor glycine supplementation affected (P > 0.05) feed intakes of pigs per kg BW. The final BW, gain:feed ratio, carcass dressing percentages, and four-lean-cuts percentages of IUGR pigs were 13.4 kg, 4.4%, 2%, and 15% lower (P < 0.05) for IUGR pigs than NBW pigs, respectively. Compared with pigs in the alanine group, dietary glycine supplementation increased (P < 0.05) final BW, gain:feed ratio, and meat a* value (a redness score) by 3.8 kg, 11%, and 10%, respectively, while reducing (P < 0.05) backfat thickness by 18%. IUGR pigs had lower (P < 0.05) concentrations of glycine in plasma (-45%), liver (-25%), jejunum (-19%), longissimus dorsi muscle (-23%), gastrocnemius muscle (-26%), kidney (-15%), and pancreas (-6%), as compared to NBW pigs. In addition, dietary glycine supplementation increased (P < 0.05) concentrations of glycine in plasma and all analyzed tissues. Thus, supplementing 1% of glycine to corn-soybean meal-based diets improves the growth performance, feed efficiency, and meat quality of IUGR pigs.

Identification of tRNA-derived small RNAs and their potential roles in porcine skeletal muscle with intrauterine growth restriction.

Intrauterine growth restriction (IUGR) in humans often manifests as poor growth and delayed intellectual development, whereas in domestic animals it results in increased mortality. As a novel epigenetic regulatory molecule, tRNA-derived small RNAs (tsRNAs) have been reported to be involved in many biological processes. In this study, pigs (35d) were used as a model to characterize tsRNAs by sequencing in normal and IUGR porcine skeletal muscle. A total of 586 tsRNAs were identified, of which 103 were specifically expressed in normal-size pigs and 38 were specifically expressed in IUGR pigs. The tsRNAs formed by splicing before the 5' end anti codon of mature tRNA (tRF-5c) accounted for over 90% of tsRNAs, which were significantly enriched in IUGR pigs than in normal-size pigs. Enriched pathways of differentially expressed tsRNAs target genes mainly included metabolic pathways, Rap1 signaling pathway, endocytosis, mTOR signaling pathway, and AMPK signaling pathway. Regulatory network analysis of target genes revealed that IGF1 was one of the most important molecules of regulatory nodes in IUGR and normal porcine skeletal muscle. In addition, IGF1 was found to be one of the target genes of tRF-Glu-TTC-047, which is a highly expressed tsRNA in IUGR pigs. The findings described herein uncover the role of tsRNAs in IUGR porcine skeletal muscle development, thus providing insights into the prevention and treatment of IUGR in mammals.

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.

Intrauterine growth restriction and its impact on intestinal morphophysiology throughout postnatal development in pigs

Intrauterine growth restriction (IUGR) compromises fetal development, leading to low birth weight, and predisposes to gastrointestinal disorders. Pigs that suffered IUGR present poor postnatal development, resulting in great economic losses to the industry. The small intestine may be involved with impaired development, but studies investigating this issue are still limited. Thus, the present study aimed to investigate small intestine morphofunctional alterations in IUGR pigs throughout the production phases (birth to 150 days). IUGR pigs presented lower body weight from birth to the finishing phase (P < 0.05). Although histomorphometrical parameters were not affected during the pre-weaning period, their commitment was observed specifically in the duodenum of the IUGR group at older ages (P < 0.05). The most detrimental effects on the small intestine, such as deeper duodenum crypts’ depth, lower villus height:crypt depth ratio and absorptive area, increased apoptosis and lower proliferation of the duodenum epithelium were noticed at 70 days of age (P < 0.05). Additionally, IUGR pigs presented the lowest chymotrypsin and amylase activities at 70 and 150 days of age, respectively (P < 0.05). These findings may contribute to the elucidation of morphofunctional disorders of the small intestine in IUGR pigs throughout the different production phases, suggesting that poor postnatal development may be due to intestinal damage.

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.

511 Late-Breaking: Dietary Glycine Supplementation During Growing and Finishing Phases Increases Body Weight and Improves Meat Quality of Intrauterine Growth Restricted Pigs

Abstract Glycine is required for maximum growth and development for growing pigs. Traditional swine diets are deficient in glycine. This is concerning for intrauterine growth restricted (IUGR) pigs (20–25% of all pigs born) as they are born with low bodyweights and underdeveloped skeletomuscular systems. Therefore, IUGR piglets are culled at birth, as they are unlikely to survive and unable to reach market weight at the same rate as normal birthweight (NBW) littermates. Additionally, IUGR pigs are not fed to market weight due to undesirable carcass attributes at slaughter such as increased subcutaneous fat deposition and decreased overall desirable protein yield. This study was designed to test the hypothesis that providing dietary glycine supplementation in traditional corn- and-soybean meal-based diets would improve the growth rate of IUGR pigs between weaning (age 21d) and market weight (age 188d). Fourteen IUGR pigs (birthweight = 0.98±0.03 kg, mean ± SEM) and 20 NBW pigs (birthweight = 1.44±0.02 kg, mean ± SEM) were obtained at weaning and used for this study. Pigs from each birthweight group were randomly assigned to 1% glycine + 0.19% corn starch treatment group or 1.19% alanine group (isonitrogenous control). Data were analyzed by using 2-way ANOVA and Duncan multiple comparison test. At 188 d of age, glycine supplemented IUGR pigs were 4.4 kg heavier (P &amp;lt; 0.05) than control IUGR pigs, and had similar (P &amp;gt;0.05) body weights to those NBW counterparts. Feed intake did not differ among the treatment groups (P &amp;gt;0.05). Additionally, glycine supplementation improved markers of meat quality in IUGR pig carcasses compared to control IUGR carcasses, including decreased backfat thickness, increased loineye area, and increased overall muscle score (P &amp;lt; 0.05). Overall, results of this study show that dietary glycine supplementation to IUGR pigs post-weaning has positive effects on lean tissue gain and meat quality. (Supported by USDA-NIFA)

510 Late-Breaking: Dietary Glycine Supplementation During Growing and Finishing Phases Increases Tissue Concentrations of Total Creatine and Gene Expression of Creatine-synthetic Enzymes in Low-birthweight Pigs

Abstract Dietary glycine is required for maximum growth and development in animals by stimulating muscle protein synthesis and as a component of creatine. Creatine is synthesized from glycine, arginine, and S-adenosylmethionine by arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT). Sufficient creatine synthesis for growth requires adequate substrate supply. However, swine diets are deficient in glycine. Additionally, intrauterine growth restricted (IUGR) pigs have reduced glycine synthesis. This results in decreased creatine synthesis and lower total creatine content in tissues, leading to reduced cellular energy metabolism and diminished muscle protein accretion. This study was designed to test the hypothesis that dietary glycine supplementation in corn-and-soybean-meal-based diets would improve overall growth and skeletal muscle accretion in post-weaning IUGR pigs by increasing the expression of creatine-synthetic enzymes and tissue concentrations of total creatine. Fourteen IUGR pigs (birthweight = 0.98±0.03 kg, mean±SEM) and 20 normal birthweight pigs (birthweight = 1.44±0.02 kg, mean±SEM) were obtained at weaning for this study. Pigs from each birthweight group were randomly assigned to 1% glycine + 0.19% corn starch treatment group or 1.19% alanine group (isonitrogenous control) for the study (21 d to 188 d of age); tissues were collected at d 188. Data were analyzed by using 2-way ANOVA and the Duncan multiple comparison test. Glycine-supplemented IUGR pigs had greater tissue concentrations of creatine, creatinine, and creatine phosphate than control IUGR in all tissues measured (P&amp;lt; 0.05). Control IUGR pigs showed diminished activity and mRNA expression of creatine-synthetic enzymes (P &amp;lt; 0.05); this was mitigated by glycine supplementation as glycine supplemented IUGR pigs showed normal levels of enzyme activity and mRNA expression. Overall, results of this study indicate dietary glycine supplementation to IUGR pigs between weaning and market weight effectively restores creatine-synthetic enzyme activities and increase tissue concentrations of total creatine, leading to increased lean tissue growth. (Supported by USDA-NIFA)

Performance and Meat Quality of Intrauterine Growth Restricted Pigs.

Simple SummaryPigs with intrauterine growth restriction (IUGR) are neonates born at term but having low birth weight and a characteristic head shape. IUGR is observed in 6-10% of pig neonates. IUGR causes problems in livestock farms due to high mortality of the piglets in the first days of life and slower postnatal growth. Tracing the surviving IUGR piglets is difficult, so the data on their post-weaning growth, performance, and carcass quality is scanty. This study shows that the post-weaning performance of IUGR pigs is poorer than that of their normal littermates. However, the growers’/fatteners’ morbidity and meat quality is not different, and the consumer preference tests clearly show that the meat of the IUGR pigs is more readily accepted than that of the normal pigs. Consumers indicated better taste, smell, and consistency of this meat. The basis of consumers preference is in a slightly different chemical composition and structure of the muscle tissue. This study shows that efforts toward reducing high mortality among IUGR neonates may be beneficial.Intrauterine growth restricted (IUGR) pigs are characterized by high perinatal mortality and dysfunction of internal organs, adipose, and muscle tissues. However, little is known about the post-weaning performance and meat quality of the IUGR pigs. The aim of this study was to compare normal pigs and pigs with IUGR from birth until slaughter, also with respect to their meat quality. Pigs with the IUGR achieved lower slaughter weight but did not differ significantly from normal pigs in terms of their meat content. The IUGR did not negatively affect the culinary quality of the obtained meat, including its content of basic chemical components and energy value, as well as hardness, chewiness, cohesiveness, elasticity, and penetration force. The meat of the IUGR pigs, when compared to the meat of normal pigs, was characterized by higher pH, lower EC (Electrical Conductivity) and drip loss; it was also tenderer and obtained higher scores in sensory evaluation of taste, smell, and general desirability. Therefore, such raw material can be appreciated by the consumers and can be used for the production of culinary portions similarly to the raw material obtained from normal pigs.

Intrauterine growth restriction alters growth performance, plasma hormones, and small intestinal microbial communities in growing-finishing pigs

BackgroundThe interaction of the gut microbiota with key metabolic and physiological processes may be associated with poor growth outcomes in animals born with intrauterine growth restriction (IUGR).ResultsGrowth performance, plasma hormone concentrations, and intestinal microbiota composition were analyzed in IUGR pigs and in normal birth weight (NBW) pigs when the NBW pigs reached 25, 50, and 100 kg of body weight (BW). Compared to NBW pigs, IUGR pigs had lower initial, weaned, and final BW, and lower average daily gain and average daily feed intake in all the considered time points. In the 25 kg BW group, IUGR pigs had higher concentrations of plasma ghrelin and pancreatic polypeptide (PP), but lower insulin concentration than NBW pigs, while the situation was reversed in the 50 kg BW group. As compared to NBW pigs, IUGR pigs had higher microbial alpha diversity in the jejunum and ileum; in the 50 and 100 kg BW groups, IUGR pigs had higher Firmicutes abundance but lower Proteobacteria abundance in the jejunum, and lower Lactobacillus abundance in the jejunum and ileum; in the 25 kg BW group, IUGR pigs showed higher unclassified Ruminococcaceae abundance in the ileum; and in 25 and 50 kg BW groups, IUGR pigs showed lower Ochrobactrum abundance in the jejunum. Spearman’s correlation revealed that Lactobacillus was negatively correlated with growth performance, while unclassified Ruminococcaceae was positively correlated. Predictive metagenomic analysis detected significantly different expression of genes in the intestinal microbiota between IUGR and NBW pigs, suggesting different metabolic capabilities between the two groups.ConclusionsGrowing-finishing IUGR pigs showed lower growth performance, higher microbial alpha diversity, and differences in plasma hormone concentrations compared to NBW pigs. Alterations in the abundance of Firmicutes, Proteobacteria, Ruminococcaceae, Lactobacillus, and Ochrobactrum in the small intestine may be associated with IUGR, and may therefore serve as a future target for gut microbiota intervention in growing-finishing IUGR pigs.

Intrauterine growth restriction in piglets alters blood cell counts and impairs cytokine responses in peripheral mononuclear cells 24 days post-partum

Large litter sizes have resulted in more piglets being exposed to intrauterine growth restriction (IUGR). Growth restriction during fetal life is linked with lower growth efficiency and increased susceptibility to infections in postnatal life and IUGR may associate with an altered innate immune system. We investigated the haematological, thromboelastography and plasma biochemical profiles of IUGR and normal piglets as well as cytokine responses in peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS) at 24 days of age. Piglets were classified at birth based on their head morphology as either IUGR or normal. The present study showed a modulation of the immune function of IUGR pigs, characterized by an increase in neutrophil percentage and fibrinogen levels but a decrease in CD4+ T-cells. A lower level of LPS-induced IL-1β production was evident in IUGR pigs, suggesting immunological hypo-responsiveness. Furthermore, higher levels of reticulocytes, MCV and MCH and lower levels of erythrocytes in IUGR pigs suggest altered bone marrow hematopoiesis. All together, the results suggest a moderate suppression of the immune response of IUGR piglets, which may have implications for resistance to pathogen challenges in the post-weaning period. Serum metabolites and blood clotting profile did not differ between IUGR and normal piglets.

Postnatal development of skeletal muscle in pigs with intrauterine growth restriction: morphofunctional phenotype and molecular mechanisms.

Intrauterine growth restriction (IUGR) is a serious condition which impairs the achievement of the fetus' full growth potential and occurs in a natural and severe manner in pigs as a result of placental insufficiency. Reduced skeletal muscle mass in the fetus with IUGR persists into adulthood and may contribute to increased metabolic disease risk. To investigate skeletal muscle postnatal development, histomorphometrical patterns of the semitendinosus muscle, myosin heavy chain (MyHC; embryonic I, IIA, IIB and IIX isoforms) fiber composition and the relative expression of genes related to myogenesis, adipogenesis and growth during three specific periods: postnatal myogenesis (newborn to 100days old), hypertrophy (100-150days old), and postnatal development (newborn to 150days old) were evaluated in female pigs with IUGR and normal birth weight (NW) female littermates. NW females presented higher body weights compared to their IUGR counterparts at all ages evaluated (P<0.05). Moreover, growth restriction in utero affected the semitendinosus muscle weight, muscle fiber diameter, and muscle cross-sectional area, which were smaller in IUGR pigs at birth (P<0.05). Notwithstanding the effects on muscle morphology, IUGR also affected muscle fiber composition, as the percentage of MyHC-I myofibers was higher at birth (P<0.05), and, in 150-day-old gilts, a lower percentage of MyHC-IIX isoform (P<0.05) and the presence of embryonic MyHC isoform were also observed. Regarding the pattern of gene expression in both the postnatal myogenesis and postnatal development periods, IUGR led to the downregulation of myogenic factors, which delayed skeletal muscle myogenesis (PAX7, MYOD, MYOG, MYF5 and DES). Altogether, growth restriction in utero affects muscle fiber number and size at birth and muscle fiber composition through the downregulation of myogenic factors, which determines the individual´s postnatal growth rate. This fact, associated with delayed myofiber development in growth-restricted animals, may affect meat quality characteristics in animal production. Hence, knowledge of the morphofunctional phenotype of the skeletal muscle throughout postnatal development in individuals with IUGR, and the mechanism that governs it, may provide a better understanding of the mechanisms that limit postnatal muscle growth, and help the establishment of potential strategies to improve muscle development and prevent the onset of later-life metabolic diseases.